Multi-stage vapor-based ablation treatment methods and vapor generation and delivery systems

ABSTRACT

Ablation catheters and systems include flexible catheter tips with a distal needle or ports for delivery of an ablative agent to a target tissue. Pressure monitoring during ablation ensure operation is performed within safe limits and with desired efficacy. Positioning elements help maintain the devices in the proper position with respect to the target tissue and also prevent the passage of ablative agent to normal tissues.

CROSS-REFERENCE

The present application relies on U.S. Patent Provisional ApplicationNo. 62/679,694, entitled “Ablation Systems and Methods” and filed onJun. 1, 2018, which is herein incorporated by reference in its entirety.

The present application relates to U.S. patent application Ser. No.15/600,670, entitled “Ablation Catheter with Integrated Cooling” andfiled on May 19, 2017, which relies on U.S. Provisional PatentApplication No. 62/425,144, entitled “Methods and Systems for Ablation”and filed on Nov. 22, 2016, and U.S. Provisional Patent Application No.62/338,871, entitled “Cooled Coaxial Ablation Catheter” and filed on May19, 2016, for priority.

The present application also relates to U.S. patent application Ser. No.15/144,768, entitled “Induction-Based Micro-Volume Heating System” andfiled on May 2, 2016, which is a continuation-in-part application ofU.S. patent application Ser. No. 14/594,444, entitled “Method andApparatus for Tissue Ablation”, filed on Jan. 12, 2015, and issued asU.S. Pat. No. 9,561,068 on Feb. 7, 2017, which is a continuation-in-partapplication of U.S. patent application Ser. No. 14/158,687, of the sametitle, filed on Jan. 17, 2014, and issued as U.S. Pat. No. 9,561,067 onFeb. 7, 2017, which, in turn, relies on U.S. Provisional PatentApplication No. 61/753,831, of the same title and filed on Jan. 17,2013, for priority.

U.S. patent application Ser. No. 14/158,687 is also acontinuation-in-part application of U.S. patent application Ser. No.13/486,980, entitled “Method and Apparatus for Tissue Ablation”, filedon Jun. 1, 2012, and issued as U.S. Pat. No. 9,561,066 on Feb. 7, 2017,which, in turn, relies on U.S. Provisional Patent Application No.61/493,344, of the same title and filed on Jun. 3, 2011, for priority.

U.S. patent application Ser. No. 13/486,980 is also acontinuation-in-part application of U.S. patent application Ser. No.12/573,939, entitled “Method and Apparatus for Tissue Ablation” andfiled on Oct. 6, 2009, which, in turn, relies on U.S. Provisional PatentApplication No. 61/102,885, of the same title and filed on Oct. 6, 2008,for priority.

All of the above referenced applications are herein incorporated byreference in their entirety.

FIELD

The present specification relates to systems and methods configured togenerate and deliver vapor for ablation therapy. More particularly, thepresent specification relates to systems and methods comprising flexiblecatheter positioning elements and/or tips with needles or ports fordelivering ablation therapy to specific organ systems.

BACKGROUND

Ablation, as it pertains to the present specification, relates to theremoval or destruction of a body tissue, via the introduction of adestructive agent, such as radiofrequency energy, laser energy,ultrasonic energy, cyroagents, or steam. Ablation is commonly used toeliminate diseased or unwanted tissues, such as, but not limited tocysts, polyps, tumors, hemorrhoids, and other similar lesions.

Steam-based ablation systems, such as the ones disclosed in U.S. Pat.Nos. 9,615,875, 9,433,457, 9,376,497, 9,561,068, 9,561,067, and9,561,066, disclose ablation systems that controllably deliver steamthrough one or more lumens toward a tissue target. One problem that allsuch steam-based ablation systems have is the potential overheating orburning of healthy tissue. Steam passing through a channel within a bodycavity heats surfaces of the channel and may cause exterior surfaces ofthe medical tool, other than the operational tool end itself, to becomeexcessively hot. As a result, physicians may unintentionally burnhealthy tissue when external portions of the device, other than thedistal operational end of the tool, accidentally contacts healthytissue. U.S. Pat. Nos. 9,561,068, 9,561,067, and 9,561,066 are herebyincorporated herein by reference.

Furthermore, the effective use of steam often requires controllablyexposing a volume of tissue to steam. However, prior art approaches tosteam ablation either fail to sufficiently enclose a volume beingtreated, thereby insufficiently exposing the tissue, or excessivelyenclose a volume being treated, thereby dangerously increasing pressureand/or temperature within the patient's organ. Pressure sensors locatedon the catheter may help regulate energy delivery, but they are notnecessarily reliable and represent a critical point of potential failurein the system.

It is therefore desirable to have steam-based ablation devices thatintegrate into the device itself safety mechanisms which preventunwanted burning during use. It is further desirable to be able toprovide a way to better control the amount of steam to which a targettissue is exposed. It is also desirable to be able to control a pressurelevel within an enclosed volume without relying on a pressure sensor inthe catheter itself. Finally, it is also desirable to providesteam-based ablation systems and methods used to treat variousconditions including pre-cancerous or cancerous tissue in the esophagus,duodenum, bile duct, and pancreas.

SUMMARY

The present specification discloses a multi-stage method for treating atleast one of excess weight, obesity, eating disorders, metabolicsyndrome, dyslipidemia, diabetes, polycystic ovarian disease, fattyliver disease, non-alcoholic fatty liver disease, or non-alcoholicsteatohepatitis disease by ablating duodenal tissue using a vaporablation system, wherein the vapor ablation system comprises acontroller having at least one processor in data communication with atleast one pump and a catheter connection port in fluid communicationwith the at least pump, the multi-stage method comprising: connecting aproximal end of a first catheter to the catheter connection port toplace the first catheter in fluid communication with the at least onepump, wherein the first catheter comprises at least two positioningelements separated along a length of the catheter and at least two portspositioned between the at least two positioning elements, wherein eachof the at least two positioning elements has a first configuration and asecond configuration, and wherein, in the first configuration, each ofthe at least two positioning elements is compressed within the catheterand in the second configuration, each of the at least two positioningelements is expanded to be at least partially outside the catheter;positioning the first catheter inside a patient such that, upon beingexpanded into the second configuration, a distal one of the at least twopositioning elements is positioned within in the patient's smallintestine and a proximal one of the at least two positioning elements isproximally positioned more than 1 cm from the distal one of the at leasttwo positioning elements; expanding each of the at least two positioningelements into their second configurations; activating the controller,wherein, upon activation, the controller is configured to cause the atleast one pump to deliver saline into at least one lumen in the firstcatheter and, wherein, upon activation, the controller is configured tocause an electrical current to be delivered to at least one electrodepositioned within the at least one lumen of the first catheter;delivering vapor through ports positioned in the first catheter betweenthe at least two positioning elements; using the controller, shuttingoff the delivery of saline and electrical current; removing the firstcatheter from the patient to complete a first stage of treating; waitingfor at least six weeks; determining an efficacy of the first phase oftreatment; depending on the determined efficacy, connecting a proximalend of a second catheter to the catheter connection port to place thesecond catheter in fluid communication with the at least one pump,wherein the second catheter comprises at least two positioning elementsseparated along a length of the catheter and at least two portspositioned between the at least two positioning elements, wherein eachof the at least two positioning elements has a first configuration and asecond configuration, and wherein, in the first configuration, each ofthe at least two positioning elements is compressed within the catheterand in the second configuration, each of the at least two positioningelements is expanded to be at least partially outside the catheter;positioning the second catheter inside a patient such that, upon beingexpanded into the second configuration, a distal one of the at least twopositioning elements is positioned within in the patient's smallintestine and a proximal one of the at least two positioning elements isproximally positioned more than 1 cm from the distal one of the at leasttwo positioning elements; expanding each of the at least two positioningelements into their second configurations; activating the controller,wherein, upon activation, the controller is configured to cause the atleast one pump to deliver saline into at least one lumen in the firstcatheter and, wherein, upon activation, the controller is configured tocause an electrical current to be delivered to at least one electrodepositioned within the at least one lumen of the first catheter;delivering vapor through ports positioned in the second catheter betweenthe at least two positioning elements; using the controller, shuttingoff the delivery of saline and electrical current; and removing thesecond catheter from the patient to complete a second stage oftreatment.

Optionally, in both the first stage of treatment and second stage oftreatment, the delivery of saline and electrical current isautomatically shut off after no more than 60 seconds.

Optionally, the method further comprises, in both the first stage oftreatment and second stage of treatment, repeatedly activating thecontroller to deliver saline into the lumen and electrical current tothe at least one electrode using at least one of a foot pedal in datacommunication with the controller, a switch on the catheter, or a switchon the controller.

Optionally, in both the first stage of treatment and second stage oftreatment, vapor is delivered such that an amount of energy in a rangeof 5 calories per second to 2500 calories per second is delivered.

Optionally, in both the first stage of treatment and second stage oftreatment, vapor is delivered such that an amount of energy in a rangeof 5 calories to 40 calories per gram of tissue to be ablated isdelivered.

Optionally, in both the first stage of treatment and second stage oftreatment, vapor is delivered such that at least fifty percent of acircumference of the small intestine is ablated.

Optionally, in the first stage of treatment, the at least twopositioning elements, together with the small intestine, define anenclosed volume and wherein at least one of the at least two positioningelements is positioned relative the small intestine to permit a flow ofair out of the enclosed volume when the vapor is delivered.

Optionally, in the second stage of treatment, the at least twopositioning elements, together with the small intestine, define anenclosed volume and wherein at least one of the at least two positioningelements is positioned relative the small intestine to permit a flow ofair out of the enclosed volume when the vapor is delivered.

Optionally, in both the first state of treatment and second stage oftreatment, the efficacy is determined by at least one of: a total bodyweight of the patient decreases by at least 1% relative to a total bodyweight of the patient before ablation; an excess body weight of thepatient decreases by at least 1% relative to an excess body weight ofthe patient before ablation; a total body weight of the patientdecreases by at least 1% relative to a total body weight of the patientbefore ablation and a well-being level of the patient does not decreasemore than 5% relative to a well-being level of the patient beforeablation; an excess body weight of the patient decreases by at least 1%relative to an excess body weight of the patient before ablation and awell-being level of the patient does not decrease more than 5% relativeto a well-being level of the patient before ablation; a pre-prandialghrelin level of the patient decreases by at least 1% relative to apre-prandial ghrelin level of the patient before ablation; apost-prandial ghrelin level of the patient decreases by at least 1%relative to a post-prandial ghrelin level of the patient beforeablation; an exercise output of the patient increases by at least 1%relative to an exercise output of the patient before ablation; aglucagon-like peptide-1 level of the patient increases by at least 1%relative to a glucagon-like peptide-1 level of the patient beforeablation; a leptin level of the patient increases by at least 1%relative to a leptin level of the patient before ablation; the patient'sappetite decreases, over a predefined period of time, relative to thepatient's appetite before ablation; a peptide YY level of the patientincreases by at least 1% relative to a peptide YY level of the patientbefore ablation; a lipopolysaccharide level of the patient decreases byat least 1% relative to a lipopolysaccharide level of the patient beforeablation; a motilin-related peptide level of the patient decreases by atleast 1% relative to a motilin-related peptide level of the patientbefore ablation; a cholecystokinin level of the patient increases by atleast 1% relative to a cholecystokinin level of the patient beforeablation; a resting metabolic rate of the patient increases by at least1% relative to a resting metabolic rate of the patient before ablation;a plasma-beta endorphin level of the patient increases by at least 1%relative to a plasma-beta endorphin level of the patient beforeablation; an HbA1c level of the patient decreases by at least 0.3%relative to an HbA1c level of the patient before ablation; atriglyceride level of the patient decreases by at least 1% relative to atriglyceride level of the patient before ablation; a total bloodcholesterol level of the patient decreases by at least 1% relative to atotal blood cholesterol level of the patient before ablation; a glycemialevel of the patient decreases by at least 1% relative to a glycemialevel of the patient before ablation; a composition of the person's gutmicrobiota modulates from a first state before ablation to a secondstate after ablation, wherein the first state has a first level ofbacteroidetes and a first level of firmicutes, wherein the second statehas a second level of bacteroidetes and a second level of firmicutes,wherein the second level of bacteroidetes is greater than the firstlevel of bacteroidetes by at least 3%, and wherein the second level offirmicutes is less than the first level of firmicutes by at least 3%;or, a cumulative daily dose of the patient's antidiabetic medicationsdecreases by at least 10% relative to a cumulative daily dose of thepatient's antidiabetic medications before ablation.

Optionally, in both the first state of treatment and second stage oftreatment, the efficacy is determined by at least one of: a lipidprofile of the patient improves by at least 10% relative a lipid profileof the patient before ablation, wherein lipid profile is defined atleast by a ratio of LDL cholesterol to HDL cholesterol, and improve isdefined as a decrease in the ratio of LDL cholesterol to HDLcholesterol; an LDL-cholesterol level of the patient decreases by atleast 10% relative to an LDL-cholesterol level of the patient beforeablation; or, a VLDL-cholesterol level of the patient decreases by atleast 10% relative to a VLDL-cholesterol level of the patient beforeablation.

Optionally, in both the first stage of treatment and second stage oftreatment, the efficacy is determined by at least one of: a 10% decreasein either ALT or AST levels relative to ALT or AST levels beforeablation; an absolute serum ferritin level of less than 1.5 ULN (upperlimit normal) relative to a serum ferritin level before ablation; lessthan 5% hepatic steatosis (HS) relative to an HS level before ablation,as measured on liver biopsy; less than 5% hepatic steatosis (HS)relative to an HS level before ablation, as measured by magneticresonance (MR) imaging, either by spectroscopy or proton density fatfraction; at least a 5% improvement in an NAFLD Fibrosis Score (NFS)relative to an NFS before ablation; at least a 5% improvement in anNAFLD Activity Score (NAS) relative to an NAS before ablation; at leasta 5% improvement in a Steatosis Activity Fibrosis (SAF) score relativeto an SAF score before ablation; at least a 5% decrease in a mean annualfibrosis progression rate relative to a mean annual fibrosis progressionrate before ablation, as measured by histology, Fibrosis-4 (FIB-4)index, aspartate aminotransferase (AST) to platelet ratio index (APRI),serum biomarkers (Enhanced Liver Fibrosis (ELF) panel, Fibrometer,FibroTest, or Hepascore), or imaging (transient elastography (TE), MRelastography (MRE), acoustic radiation force impulse imaging, orsupersonic shear wave elastography); at least a 5% decrease incirculating levels of cytokeratin-18 fragments relative to circulatinglevels of cytokeratin-18 fragments before ablation; at least a 5%decrease in liver stiffness relative to liver stiffness before ablation,as measured by vibration controlled transient elastography(VCTE/FibroScan); an improvement in NAS by at least 2 points, with atleast 1-point improvement in hepatocellular ballooning and at least1-point improvement in either lobular inflammation or steatosis score,and no increase in the fibrosis score, relative to NAS, hepatocellularballooning, lobular inflammation, steatosis, and fibrosis scores beforeablation; at least a 5% improvement in NFS scores relative to NFS scoresbefore ablation; or, at least a 5% improvement in any of the abovelisted NAFLD parameters as compared to a sham intervention or a placebo.

The present specification also discloses a multi-stage method fortreating cancerous or precancerous esophageal tissue by ablating thecancerous or precancerous esophageal tissue using a vapor ablationsystem, wherein the vapor ablation system comprises a controller havingat least one processor in data communication with at least one pump anda catheter connection port in fluid communication with the at leastpump, the multi-stage method comprising: connecting a proximal end of afirst catheter to the catheter connection port to place the firstcatheter in fluid communication with the at least one pump, wherein thefirst catheter comprises at least two positioning elements separatedalong a length of the catheter and at least two ports positioned betweenthe at least two positioning elements, wherein each of the at least twopositioning elements has a first configuration and a secondconfiguration, and wherein, in the first configuration, each of the atleast two positioning elements is compressed within the catheter and inthe second configuration, each of the at least two positioning elementsis expanded to be at least partially outside the catheter; positioningthe first catheter inside a patient such that, upon being expanded intothe second configuration, a distal one of the at least two positioningelements is positioned adjacent the patient's esophagus and a proximalone of the at least two positioning elements is proximally positionedmore than 1 cm from the distal one of the at least two positioningelements; expanding each of the at least two positioning elements intotheir second configurations; activating the controller, wherein, uponactivation, the controller is configured to cause the at least one pumpto deliver saline into at least one lumen in the first catheter and,wherein, upon activation, the controller is configured to cause anelectrical current to be delivered to at least one electrode positionedwithin the at least one lumen of the first catheter; delivering vaporthrough ports positioned in the first catheter between the at least twopositioning elements; using the controller, shutting off the delivery ofsaline and electrical current; removing the first catheter from thepatient to complete a first stage of treating; waiting for at least sixweeks; determining an efficacy of the first phase of treatment;depending upon the efficacy determination, connecting a proximal end ofa second catheter to the catheter connection port to place the secondcatheter in fluid communication with the at least one pump, wherein thesecond catheter comprises a distal tip having at least one port and atleast one positioning element attached to the distal tip such that, uponbeing in an operational configuration, the at least one positioningelement encircles the at least one port and is configured to direct allvapor exiting from the at least one port; positioning the secondcatheter inside the patient such that a distal surface of the at leastone positioning element is positioned adjacent the patient's esophagus;activating the controller, wherein, upon activation, the controller isconfigured to cause the at least one pump to deliver saline into atleast one lumen in the second catheter and, wherein, upon activation,the controller is configured to cause an electrical current to bedelivered to at least one electrode positioned within the at least onelumen of the second catheter; delivering vapor through the at least oneport positioned at the distal end of the second catheter; using thecontroller, shutting off the delivery of saline and electrical current;and removing the second catheter from the patient to complete a secondstage of treatment.

Optionally, in both the first stage of treatment and second stage oftreatment, the delivery of saline and electrical current isautomatically shut off after no more than 60 seconds.

Optionally, the method further comprises, in both the first stage oftreatment and second stage of treatment, repeatedly activating thecontroller to deliver saline into the lumen and electrical current tothe at least one electrode using at least one of a foot pedal in datacommunication with the controller, a switch on the catheter, or a switchon the controller.

Optionally, in both the first stage of treatment and second stage oftreatment, vapor is delivered such that an amount of energy in a rangeof 5 calories per second to 2500 calories per second is delivered.

Optionally, in both the first stage of treatment and second stage oftreatment, vapor is delivered such that an amount of energy in a rangeof 5 calories to 40 calories per gram of tissue to be ablated isdelivered.

Optionally, in both the first stage of treatment and second stage oftreatment, vapor is delivered such that at least fifty percent of acircumference of the small intestine is ablated.

Optionally, in the first stage of treatment, the at least twopositioning elements, together with the esophageal tissue, define anenclosed volume wherein at least one of the at least two positioningelements is positioned relative the esophageal tissue to permit a flowof air out of the enclosed volume when the vapor is delivered.

Optionally, in the second stage of treatment, the at least onepositioning element, together with the esophageal tissue, defines anenclosed volume and wherein the at least one positioning element ispositioned relative the esophageal tissue to permit a flow of air out ofthe enclosed volume when the vapor is delivered.

The present specification also discloses a flexible heating chamberconfigured to be incorporated into a tip of a catheter, the flexibleheating chamber comprising: an outer covering; an inner core coaxial tosaid outer covering; a first array of electrodes disposed between saidouter covering and said inner core, wherein said first array ofelectrodes comprise a first metal ring having a plurality of first fins;and a second array of electrodes disposed between said outer coveringand said inner core, wherein said second array of electrodes comprises asecond metal ring having a plurality of second fins, and wherein saidfirst and second fins interdigitate with each other such that asegmental space separates each of said first and second fins.

Optionally, said plurality of first and second fins extend radially intoa space between said outer covering and said inner core, and whereinsaid plurality of first and second fins also extend along a longitudinalaxis of the heating chamber.

Optionally, each of said plurality of first and second fins has a firstdimension along a radius of the heating chamber and a second dimensionalong a longitudinal axis of the heating chamber.

Optionally, water or saline flows through said segmental spaces andelectrical current is provided to said first and second array ofelectrodes causing said first and second fins to generate heat andvaporize said water or saline into steam.

Optionally, the heating chamber has a width ranging from 1 to 5 mm and alength ranging from 5 to 50 mm.

Optionally, the first array of electrodes has a range of 1 to 50 finsand the second array of electrodes has a range of 1 to 50 fins.

Optionally, said segmental space ranges from 0.01 to 2 mm.

The present specification also discloses a catheter for performingablation of target tissue and having a body with a proximal end, adistal end, a first lumen and a second lumen, said catheter comprising:a proximal balloon and a distal balloon positioned proximate the distalend of the body; a plurality of ports located on the body between saidproximal and distal balloons; and a first flexible heating chamberincorporated in the second lumen and placed proximate to the proximalballoon, said first flexible heating chamber comprising: an outercovering; an inner core coaxial to said outer covering; a first array ofelectrodes disposed between said outer covering and the inner core,wherein said first array of electrodes comprise a first metal ringhaving a plurality of first fins; and a second array of electrodesdisposed between said outer covering and said inner core, wherein saidsecond array of electrodes comprises a second metal ring having aplurality of second fins, and wherein said first and second finsinterdigitate with each other such that a first segmental spaceseparates each of said first and second fins.

Optionally, a first pump coupled to the proximal end of the body propelsair through the first lumen to inflate the proximate and distalballoons, a second pump coupled to the proximal end of the body propelswater or saline through the second lumen to supply said water or salineto a proximal end of the first heating chamber, and an RF generatorcoupled to the proximal end of the body supplies electrical current tosaid first and second array of electrodes causing said first and secondfins to generate heat and vaporize said water or saline into steam fordelivery to the target tissue through said ports.

Optionally, said plurality of first and second fins extend radially intoa space between said outer covering and said inner core of the firstheating chamber, and wherein said plurality of first and second finsalso extend along a longitudinal axis of the first heating chamber.

Optionally, each of said plurality of first and second fins has a firstdimension along a radius of the first heating chamber and a seconddimension along a longitudinal axis of the first heating chamber.

Optionally, the catheter further comprises a second flexible heatingchamber arranged in series with said flexible heating chamber, whereinthe second flexible heating chamber comprises: an outer covering; aninner core coaxial to the outer covering; a third array of electrodesdisposed between the outer covering and the inner core, wherein thethird array of electrodes comprise a third metal ring having a pluralityof third fins; and a fourth array of electrodes disposed between theouter covering and the inner core, wherein said fourth array ofelectrodes comprises a fourth metal ring having a plurality of fourthfins, and wherein the third and fourth fins interdigitate with eachother such that a second segmental space separates each of said thirdand fourth fins.

Optionally, the plurality of third and fourth fins extend radially intoa space between said outer covering and the inner core of the secondheating chamber and said plurality of third and fourth fins also extendalong a longitudinal axis of the second heating chamber.

Optionally, each of said plurality of third and fourth fins has a firstdimension along a radius of the second heating chamber and a seconddimension along a longitudinal axis of the second heating chamber.

Optionally, each of said first and second heating chambers has a widthranging from 1 to 5 mm and a length ranging from 5 to 50 mm.

Optionally, the first and third array of electrodes have a range of 1 to50 fins and the second and fourth array of electrodes have a range of 1to 50 fins.

Optionally, said first and second segmental spaces range from 0.01 to 2mm.

The present specification also discloses a method of performing ablationof Barrett's esophagus tissue, comprising: inserting a catheter into anesophagus of a patient, said catheter having a body with a proximal end,a distal end, a first lumen and a second lumen, wherein the cathetercomprises: a proximal balloon and a distal balloon positioned proximatethe distal end of the body; a plurality of ports located on the bodybetween said proximal and distal balloons; and at least one flexibleheating chamber incorporated in the second lumen and placed proximate tothe proximal balloon, said at least one flexible heating chambercomprising: an outer covering; an inner core coaxial to said outercovering; a first array of electrodes disposed between said outercovering and said inner core, wherein said first array of electrodescomprise a first metal ring having a plurality of first fins; and asecond array of electrodes disposed between said outer covering and saidinner core, wherein said second array of electrodes comprises a secondmetal ring having a plurality of second fins, and wherein said first andsecond fins interdigitate with each other such that a first segmentalspace separates each of said first and second fins; positioning thedistal balloon distal to a portion of Barrett's esophagus and theproximal balloon proximal to a portion of Barrett's esophagus such thatthe ports are positioned in said portion of Barrett's esophagus;inflating the proximal and distal balloons to position the catheter inthe esophagus; providing water or saline to the catheter; and providingelectric current to said first and second array of electrodes causingsaid first and second fins to generate heat and vaporize said water orsaline into steam, wherein said steam is delivered through said ports toablate the Barrett's esophagus tissue.

Optionally, a first pump coupled to the proximal end of the body propelsair through the first lumen to inflate the proximate and distalballoons, a second pump coupled to the proximal end of the body propelswater or saline through the second lumen to supply said water or salineto a proximal end of the heating chamber, and an RF generator coupled tothe proximal end of the body supplies electrical current to said firstand second array of electrodes.

Optionally, each of said plurality of first and second fins has a firstdimension along a radius of the heating chamber and a second dimensionalong a longitudinal axis of the heating chamber.

The present specification also discloses a method of ablating apancreatic tissue, comprising: providing an ablation device comprising:an echoendoscope; a catheter having a needle at a distal end andconfigured pass within a channel of said echoendoscope to deliver vaporto said pancreatic tissue; a controller programmed to determine anamount of thermal energy needed to ablate said pancreatic tissue,programmed to limit a maximum dose of said ablative agent based on atype of disorder being treated, and programmed to limit the amount ofthermal energy delivered such that a pressure within the patient'spancreas does not exceed 5 atm; advancing said echoendoscope into agastrointestinal tract of a patient and proximate said pancreatictissue; localizing said pancreatic tissue using said echoendoscope;advancing said catheter through said channel of said echoendoscope suchthat said needle passes through a gastrointestinal wall at a puncturesite and enters into said pancreatic tissue; and delivering vaporthrough said needle into said pancreatic tissue for ablation.

Optionally, the method further comprises the steps of: measuring atleast one dimension of said pancreatic tissue using said echoendoscope;and said controller using said at least one measured dimension tocalculate an amount of vapor to deliver.

Optionally, the method further comprises applying suction to said needleprior to delivering vapor to aspirate fluid and/or cells from saidprostatic tissue.

Optionally, said needle comprises an outer sheath and said methodfurther comprises circulating water through said outer sheath as vaporis delivered to cool said puncture site.

Optionally, the method further comprises using said echoendoscope toobserve said pancreatic tissue as ablation is performed and stoppingsaid ablation once adequate ablation has been achieved as per visualobservation.

Optionally, ablation is terminated after a pressure measured in saidpancreas remains in a range of 0.1 to 5 atm for a time period of atleast 1 second. Optionally, the method further comprises deliveringvapor again after ablation has been terminated for at least a timeperiod of 1 second.

Optionally, ablation is stopped when a pressure measured in saidablation device exceeds 5 atm.

Optionally, a temperature of said pancreatic tissue is in a range of100° C. to 110° C. for at least a portion of the ablation procedure.

Optionally, said ablation device further comprises a pressure sensor.

Optionally, said ablation device further comprises a temperature sensor.

The present specification also discloses a method of ablating pancreatictissue comprising the steps of: providing an ablation device comprising:a catheter having a hollow shaft and a retractable needle through whichan ablative agent can travel; at least one infusion port on said needlefor the delivery of said ablative agent to said upper gastrointestinaltract tissue; at least one sensor for measuring at least one parameterof said catheter; and a controller comprising a microprocessor forcontrolling the delivery of said ablative agent; inserting anechoendoscope into an upper gastrointestinal tract of a patient;identifying the pancreatic tissue to be ablated using saidechoendoscope; passing said catheter through said echoendoscope suchthat said at least one distal positioning element is positioned proximalto said pancreatic tissue to be ablated in the gastrointestinal tract;extending said needle through the catheter in the upper gastrointestinaltract lumen of said patient such that said infusion port is positionedwithin said pancreatic tissue of said patient; operating said at leastone sensor to measure at least one parameter of said catheter; usingsaid at least one parameter measurement to control the flow of ablativeagent to deliver to said pancreatic tissue; and delivering said ablativeagent through said at least one infusion port to ablate said pancreatictissue.

The present specification also discloses a device for use with anendoscope for hot fluid ablation comprising: an elongate tubular memberhaving a length and a lumen for conveying the hot fluid from a proximalend to a distal end, the distal end being open and adapted to sprayvapor at a temperature and low pressure at a target tissue; and aninsulating element covering at least a portion of the device; wherein anouter diameter of the device is configured to allow passage of thedevice through the endoscope.

Optionally, the hot fluid is steam or vapor. Optionally, the temperatureranges from 65 C to 150 C. Optionally, the pressure is <5 atm.Optionally, the insulating element is heat resistant polymer.

The present specification also discloses a catheter for use in anablation procedure comprising: a tubular member having an inner surfacedefining a channel for ablative fluid flow, a proximal end for receivingablative fluid from a source, and a distal end being adapted to spraylow pressure ablative agent at a target tissue; and an insulatingelement disposed longitudinally along at least a portion of the lengthof the tubular member.

The present specification also discloses a catheter for use with anendoscope in a thermal ablation procedure, the catheter comprising: atubular member having a proximal end for receiving an ablative agent, anopen distal end adapted to spray low pressure ablative agent at a targettissue, an inside surface comprising a heat resistant polymer defining achannel and configured to contact ablative agent flowing from theproximal end to the distal end; and a cooling element disposedlongitudinally along at least a portion of an outer surface.

The present specification also discloses a vapor ablation apparatus forvapor spray ablation, comprising: an endoscope; a catheter having adistal end, wherein the catheter is disposed within the endoscope; and asource of vapor attached to the catheter by a conduit, wherein theapparatus is configured such that, in use, high temperature, lowpressure vapor exits the catheter distal end, and wherein the distal endof the catheter is adapted to spray vapor in a radial directionsubstantially perpendicular to the axis of the catheter.

The present specification also discloses a vapor spray apparatus forvapor spray ablation, comprising: an endoscope having a distal endprovided with a lens, such that the endoscope is used to locate thetarget tissue; a catheter having a distal end, said catheter beingconnected to the endoscope and carried thereby; a source of vaporconnected to the catheter by a conduit and disposed externally of thepatient; wherein the apparatus is configured such that, in use, hightemperature, low pressure vapors exits the catheter distal end.

The present specification also discloses a method of ablating a hollowtissue or a hollow organ comprising the steps of: replacing the naturalcontents of the hollow tissue or the organ with a conductive medium; anddelivering an ablative agent to the conductive medium to ablate thetissue or organ.

The present specification also discloses a device for ablationcomprising a port for delivering a conductive medium and a source ofablative agent.

Optionally, said ablation comprises one of cryoablation or thermalablation.

Optionally, the device comprises ports to remove the content of thehollow organ or the conductive medium.

The present specification also discloses a method of ablating a bloodvessel comprising the steps of: replacing a blood in a targeted vesselwith a conductive medium; and delivering an ablative agent to theconductive medium to ablate the desired blood vessel.

Optionally, the method further comprises stopping a flow of blood intothe target blood vessel. Optionally, the blood flow is occluded byapplication of a tourniquet. Optionally, the blood flow is occluded byapplication of an intraluminal occlusive element. Optionally, theintraluminal occlusive element comprises unidirectional valves.

Optionally, sensors are used to control a flow of the ablative agent.

Optionally, the conductive medium is one of water or saline.

The present specification also discloses a device for ablating a bloodvessel comprising a catheter with a proximal end and a distal end,wherein the proximal end is operably connected to the distal end, a portat the distal end for infusion of a conductive medium for replacing ablood in a target vessel with a conductive medium, and a source at thedistal end for delivering an ablative agent to said conductive medium.

Optionally, the device further comprises an occlusive element torestrict a flow of blood or the conductive medium. Optionally, theocclusive element comprises unidirectional valves. Optionally, theocclusive element is used to position the source of the ablative agentin the blood vessel.

Optionally, the device further comprises suction ports for removal ofblood or the conductive medium.

Optionally, the device further comprises a sensor to measure a deliveryof ablative agent, flow of blood or an ablation parameter.

The present specification also discloses a method of ablating a bloodvessel wall comprising the steps of placing a catheter in a segment ofthe blood vessel, occluding a flow of blood to the segment of the bloodvessel, replacing a portion of a blood in the segment with a conductivemedium, adding an ablative agent into the conductive medium, andconducting ablative energy to the blood vessel wall through theconductive medium to cause ablation of said blood vessel wall.

The present specification also discloses a device for ablating a bloodvessel comprising a coaxial catheter with a proximal end and a distalend, an outer sheath, an inner tubular member, at least one port forinfusing a conductive medium, a source for delivery of an ablativeagent, and at least one occlusive element configured to restrict a flowof blood and position the source of ablative agent in the blood vessel,wherein at least the outer sheath of the coaxial catheter is made of aninsulating material.

The present specification also discloses a method of ablating a cystcomprising the steps of: providing an ablation device comprising acatheter having a handle at a proximal end and needle at a distal end;passing said catheter into a patient and advancing said catheter to saidcyst; inserting said needle into said cyst; applying suction to saidcatheter to remove at least a portion of the contents of said cyst;injecting a conductive medium into said cyst through said needle;delivering an ablative agent through into said conductive medium throughsaid needle; and applying suction to said catheter to remove saidconductive medium and said ablative agent.

The present specification also discloses a method of ablating a cystcomprising the steps of placing a catheter in the cyst, replacing aportion of the contents in the cyst with a conductive medium, adding anablative agent into the conductive medium, and conducting ablativeenergy to a cyst wall through the conductive medium to cause ablation ofsaid cyst.

The present specification also discloses a device for ablating a cystcomprising a coaxial catheter with a proximal end and a distal end, anouter sheath, an inner tubular member, at least one port for infusing aconductive medium, a source for delivery of an ablative agent, and atleast one port for removal of the contents of the cyst, wherein at leastthe outer sheath of the coaxial catheter is made of an insulatingmaterial.

Optionally, the device further comprises a sensor to control thedelivery of the ablative agent or for measurement of an ablation effect.

Optionally, the catheter comprises echogenic elements to assist with theplacement of the catheter into the cyst under ultrasound guidance.

Optionally, the catheter comprises radio-opaque elements to assist withthe placement of the catheter into the cyst under radiological guidance.

The present specification also discloses a method of ablating a solidtumor comprising the steps of placing a catheter in the tumor,instilling a conductive medium into the tumor, adding an ablative agentinto the conductive medium, and conducting ablative energy to the tumorthrough the conductive medium to cause ablation of the tumor.

The present specification also discloses a device for ablating a tumorcomprising an insulated catheter with a proximal end and a distal end,at least one port for infusing a conductive medium, and a source fordelivery of an ablative agent.

Optionally, the device further comprises a sensor to control thedelivery of the ablative agent or for measurement of an ablation effect.

Optionally, the catheter comprises echogenic elements to assist with theplacement of the catheter into the cyst under ultrasound guidance.

Optionally, the catheter comprises radio-opaque elements to assist withthe placement of the catheter into the cyst under radiological guidance.

The present specification also discloses a method of ablating tissuecomprising the steps of: providing an ablation device comprising: athermally insulating catheter having a hollow shaft and a retractableneedle through which an ablative agent can travel; at least one infusionport on said needle for the delivery of said ablative agent to saidtissue; and a controller comprising a microprocessor for controlling thedelivery of said ablative agent; passing said catheter and extending thesaid needle with the said at least one infusion port so the needle andthe infusion port are positioned within said tissue of said patient; anddelivering said ablative agent through said at least one infusion portto ablate said tissue.

Optionally, said ablation device further comprises at least one sensorfor measuring at least one parameter of said tissue and said methodfurther comprises the steps of: operating said at least one sensor tomeasure at least one parameter of said tissue; and using said at leastone parameter to determine the amount of ablative agent to deliver tosaid tissue.

Optionally, said ablation device further comprises at least one sensorfor measuring at least one parameter of said catheter and said methodfurther comprises the steps of: operating said at least one sensor tomeasure at least one parameter of said catheter; and using said at leastone parameter to turn-off the delivery of ablative agent to said tissue.

Optionally, said at least one sensor comprises a temperature, pressure,infrared, electromagnetic, acoustic, or radiofrequency energy emitterand sensor.

Optionally, said catheter comprises at least one distal positioningelement configured such that, once said positioning element is deployed,said catheter is positioned proximate said tissue for ablation.Optionally, said at least one positioning element is any one of aninflatable balloon, a wire mesh disc, a cone shaped attachment, a ringshaped attachment, or a freeform attachment. Optionally, saidpositioning element is covered by an insulated material to prevent theescape of thermal energy beyond said tissue to be ablated.

Optionally, said at least one distal positioning element is separatedfrom tissue to be ablated by a distance of greater than 0.1 mm.

Optionally, said delivery of said ablative agent is guided bypredetermined programmatic instructions.

Optionally, said ablation device further comprises at least one sensorfor measuring a parameter of said tissue and said method furthercomprises the steps of: operating said at least one sensor to measure aparameter of said tissue; and using said parameter measurement tocontrol a flow of said ablative agent to said tissue.

Optionally, said sensor is any one of a temperature, pressure, photo, orchemical sensor.

Optionally, said ablation device further comprises a coaxial memberconfigured to restrain said at least one positioning element and saidstep of deploying said at least one distal positioning element furthercomprises removing said coaxial member from said ablation device.

Optionally, said catheter further comprises at least one suction portand said method further comprises operating said at least one suctionport to remove ablated tissue from the body.

Optionally, said ablation device further comprises an input device andsaid method further comprises the step of an operator using said inputdevice to control the delivery of said ablative agent.

Optionally, said tissue is a cyst.

The present specification also discloses a method of ablating tissuecomprising the steps of: providing an ablation device comprising: acatheter having a hollow shaft and a retractable needle through which anablative agent can travel; at least one distal positioning elementattached to a distal tip of said catheter; at least one infusion port onsaid needle for the delivery of said ablative agent to said tissue, saidat least one infusion port configured to deliver said ablative agentinto a space defined by said distal positioning element; and acontroller comprising a microprocessor for controlling the delivery ofsaid ablative agent; inserting said catheter such that said at least onepositioning element is positioned proximate said tissue to be ablated;extending the needle through the catheter such that the infusion port ispositioned proximate to the tissue; and delivering said ablative agentthrough said at least one infusion port to ablate said tissue.

Optionally, said ablation device further comprises at least one inputport on said catheter for receiving said ablative agent.

Optionally, said tissue is a pancreatic cyst.

The present specification also discloses a method for providing ablationtherapy to a patient's gastrointestinal tract comprising: insertingablation catheter into the gastrointestinal tract, wherein the ablationcatheter comprises at least one positioning element and a port for thedelivery of vapor; creating a seal between an exterior surface of the atleast one positioning element and a wall of the gastrointestinal tract,forming an enclosed volume in the gastrointestinal tract; deliveringvapor through the ablation catheter into the enclosed volume; andcondensing the vapor on a tissue within the gastrointestinal tract.

Optionally, the seal is temperature dependent. Optionally, the sealbreaks when temperature inside the enclosed volume exceeds 90 degreescentigrade.

Optionally, the seal is pressure dependent. Optionally, the seal breakswhen pressure inside the enclosed volume exceeds 5 atm.

The present specification also discloses a method for providing ablationtherapy to a patient's gastrointestinal tract comprising: inserting anablation catheter into the gastrointestinal tract; initiating a flow ofsaline through the ablation catheter, wherein the flow rate of saline isvariable; heating the saline by delivering RF energy to the saline togenerate vapor; delivering vapor through the ablation catheter into thegastrointestinal tract; and condensing the vapor on a tissue within thegastrointestinal tract.

Optionally, the flow rate of saline during heat therapy is differentfrom flow rate of saline during the phase where no heat therapy isdelivered.

Optionally, the flow rate of saline during heat therapy is higher fromflow rate of saline during the phase where no heat therapy is delivered.

Optionally, the flow rate of saline during heat therapy is lower fromflow rate of saline during the phase where no heat therapy is delivered.

The present specification also discloses a method for ablating a tissue,comprising: inserting a first ablation catheter into a patient'sgastrointestinal (GI) tract, wherein the first ablation cathetercomprises a distal positioning element, a proximal positioning element,and a plurality of vapor delivery ports between the distal and proximalpositioning elements; expanding the distal positioning element;expanding the proximal positioning element to create a first sealbetween the peripheries of the distal and proximal positioning elementsand the GI tract and form a first enclosed treatment volume between thedistal and proximal positioning elements and a surface of the patient'sGI tract; delivering vapor via the delivery ports; allowing the vapor tocondense on tissue within the first enclosed treatment volume tocircumferentially ablate the tissue; removing the first ablationcatheter from the GI tract; examining an area of tissue ablated by thefirst ablation catheter to identify patches of tissue requiring focusedablation; inserting a second ablation catheter into the GI tract throughan endoscope, wherein the second ablation catheter comprises a distalattachment or positioning element and at least one delivery port at adistal end of the catheter; expanding the distal attachment orpositioning element to create a second seal between the periphery of thedistal attachment or positioning element and the GI tract and form asecond enclosed treatment volume between the distal attachment orpositioning element and the surface of the patient's GI tract;delivering vapor via the at least one port; allowing the vapor tocondense on the tissue within the second enclosed treatment volume tofocally ablate the tissue; and removing the second ablation catheterfrom the GI tract.

The aforementioned and other embodiments of the present invention shallbe described in greater depth in the drawings and detailed descriptionprovided below.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other features and advantages of the present invention will befurther appreciated, as they become better understood by reference tothe detailed description when considered in connection with theaccompanying drawings, wherein:

FIG. 1A illustrates an ablation system, in accordance with embodimentsof the present specification;

FIG. 1B is a transverse cross-section view of a flexible heatingchamber, in accordance with an embodiment of the present specification;

FIG. 1C illustrates transverse and longitudinal cross-section views offirst and second arrays of electrodes of a flexible heating chamber, inaccordance with an embodiment of the present specification;

FIG. 1D is a transverse cross-section view of the heating chamber ofFIG. 1B, including assembled first and second arrays of electrodes, inaccordance with an embodiment of the present specification;

FIG. 1E is a longitudinal cross-section view of the heating chamber ofFIG. 1B, including assembled first and second arrays of electrodes, inaccordance with an embodiment of the present specification;

FIG. 1F is a first longitudinal view of two heating chambers of FIG. 1Barranged in series in a catheter tip, in accordance with an embodimentof the present specification;

FIG. 1G is a second longitudinal view of two heating chambers of FIG. 1Barranged in series in a catheter tip, in accordance with an embodimentof the present specification;

FIG. 1H illustrates a multiple lumen balloon catheter incorporating oneheating chamber of FIG. 1B, in accordance with an embodiment of thepresent specification;

FIG. 1I illustrates a multiple lumen balloon catheter incorporating twoheating chambers of FIG. 1B, in accordance with an embodiment of thepresent specification;

FIG. 1J is a flow chart of a plurality of steps of using the catheter ofFIG. 1H or FIG. 1I to perform ablation of Barrett's esophagus tissue inan esophagus of a patient, in accordance with an embodiment of thepresent specification;

FIG. 1K illustrates a catheter with proximal and distal positioningelements and an electrode heating chamber, in accordance withembodiments of the present specification;

FIG. 1L is a flow chart illustrating a method of ablating a tissueinside a gastrointestinal tract of a patient, in accordance with someembodiments of the present specification;

FIG. 1M is a flow chart illustrating a method of ablating a tissueinside a gastrointestinal tract of a patient, in accordance with otherembodiments of the present specification;

FIG. 1N is a flow chart illustrating a method for treating agastrointestinal condition in a patient using a vapor ablation system,in accordance with embodiments of the present specification;

FIG. 2A shows perspective views of a needle ablation device, inaccordance with an embodiment of the present specification;

FIG. 2B shows a cross-sectional view of the needle ablation device ofFIG. 2A, in accordance with an embodiment of the present specification;

FIG. 2C shows a first enlarged cross-sectional view of the needleablation device of FIG. 2A, in accordance with an embodiment of thepresent specification;

FIG. 2D shows a second enlarged cross-sectional view of the needleablation device of FIG. 2A, in accordance with an embodiment of thepresent specification;

FIG. 3A shows perspective views of an endoscope and of the needleablation device of FIG. 2A being deployed through the endoscope, inaccordance with an embodiment of the present specification;

FIG. 3B shows a perspective view of a bending section of the endoscope,in accordance with an embodiment of the present specification;

FIG. 4A shows a perspective view of a needle of a needle ablationdevice, in accordance with an embodiment of the present specification;

FIG. 4B shows another perspective view of the needle of the needleablation device of FIG. 4A, in accordance with an embodiment of thepresent specification;

FIG. 4C shows cross-sectional views of the needle of the needle ablationdevice of FIG. 4A, in accordance with a first embodiment of the presentspecification;

FIG. 4D shows cross-sectional views of the needle of the needle ablationdevice of FIG. 4A, in accordance with a second embodiment of the presentspecification;

FIG. 4E shows perspective views of various needles illustrating theneedle tip portions and insulating coatings, in accordance withembodiments of the present specification;

FIG. 5A shows perspective views of a needle of a needle ablationcatheter having variable stiffness along its length, in accordance withan embodiment of the present specification;

FIG. 5B shows perspective views of a plurality of needles of a needleablation catheter having variable stiffness along their lengths, inaccordance with some embodiments of the present specification;

FIG. 5C shows first and second needles of needle ablation cathetershaving different laser cut portions, in accordance with some embodimentsof the present specification;

FIG. 5D shows a plurality of laser cutting patterns for a needle of aneedle ablation catheter, in accordance with some embodiments of thepresent specification;

FIG. 6A is a first cross-sectional view of a catheter for insertion intoa needle of the needle ablation device of FIG. 2A, in accordance with anembodiment of the present specification;

FIG. 6B is a second cross-sectional view of the catheter of FIG. 6A, inaccordance with an embodiment of the present specification;

FIG. 6C illustrates a first plurality of configurations of an expandabletip of the catheter of FIG. 6A, in accordance with some embodiments ofthe present specification;

FIG. 6D illustrates a second plurality of configurations of theexpandable tip of the catheter of FIG. 6A, in accordance with someembodiments of the present specification;

FIG. 7A illustrates the ablation device with a coaxial catheter design,in accordance with an embodiment of the present specification;

FIG. 7B illustrates a partially deployed positioning device, inaccordance with an embodiment of the present specification;

FIG. 7C illustrates a completely deployed positioning device, inaccordance with an embodiment of the present specification;

FIG. 7D illustrates the ablation device with a conical positioningelement, in accordance with an embodiment of the present specification;

FIG. 7E illustrates the ablation device with a disc shaped positioningelement, in accordance with an embodiment of the present specification;

FIG. 8A illustrates a conical hood shaped positioning element, inaccordance with an embodiment of the present specification;

FIG. 8B illustrates a cross-sectional view of the conical hood shapedpositioning element, in accordance with an embodiment of the presentspecification;

FIG. 8C illustrates a ball and socket attachment of the conical hoodshaped positioning element to a catheter tip, in accordance with anembodiment of the present specification;

FIG. 8D illustrates cross-sectional views of the conical hood shapedpositioning element attached to the catheter tip, in accordance with anembodiment of the present specification;

FIG. 8E illustrates perspective views of the conical hood shapedpositioning element attached to the catheter tip, in accordance with anembodiment of the present specification;

FIG. 8F shows a first configuration of the conical hood shapedpositioning element, in accordance with an embodiment of the presentspecification;

FIG. 8G shows a second configuration of the conical hood shapedpositioning element, in accordance with an embodiment of the presentspecification;

FIG. 8H shows a third configuration of the conical hood shapedpositioning element, in accordance with an embodiment of the presentspecification;

FIG. 8I shows a fourth configuration of the conical hood shapedpositioning element having a pyramidal base, in accordance with anembodiment of the present specification;

FIG. 8J illustrates an ablation catheter with a conical shapedattachment or positioning element and an electrode heating chamber, inaccordance with some embodiments of the present specification;

FIG. 9A is a flow chart illustrating a method of ablating a tissueinside a gastrointestinal tract of a patient, in accordance with someembodiments of the present specification;

FIG. 9B is a flow chart illustrating a method of ablating a tissueinside a gastrointestinal tract of a patient, in accordance with otherembodiments of the present specification;

FIG. 9C is a flow chart illustrating a method of using a first ablationcatheter to perform circumferential ablation and then a second ablationcatheter to perform focal ablation, in accordance with some embodimentsof the present specification;

FIG. 9D is a flow chart illustrating a multi-phase method of using avapor ablation system for duodenal ablation in order to treat obesity,excess weight, eating disorders, metabolic syndrome, diabetes,dyslipidemia, non-alcoholic steatohepatitis (NASH), non-alcoholic fattyliver disease (NAFLD), or a polycystic ovary disease, in accordance withembodiments of the present specification;

FIG. 9E is a flow chart illustrating a multi-stage method of using avapor ablation system for treating cancerous or precancerous esophagealtissue, in accordance with various embodiments of the presentspecification;

FIG. 10A shows first and second graphs illustrating energy consumptionprofile by a heating chamber (flexible heating chamber with RFelectrodes or inductive coil based heating chamber) and pressure profileof vapor generated during an ablation therapy, in accordance with anembodiment of the present specification;

FIG. 10B illustrates an alert being generated when vapor pressure at theheating chamber reaches above a predefined limit, in accordance with anembodiment of the present specification;

FIG. 10C shows third and fourth graphs illustrating a temperatureprofile of vapor and a pressure profile of vapor generated during anablation therapy, in accordance with an embodiment of the presentspecification;

FIG. 10D illustrates a first pressure therapy profile, in accordancewith an embodiment of the present specification;

FIG. 10E illustrates a plurality of cycles of the first pressure therapyprofile, in accordance with an embodiment of the present specification;

FIG. 10F illustrates a plurality of cycles of the first pressure therapyprofile, in accordance with another embodiment of the presentspecification;

FIG. 10G illustrates a second pressure therapy profile, in accordancewith an embodiment of the present specification;

FIG. 10H illustrates the second pressure therapy profile, in accordancewith another embodiment of the present specification;

FIG. 10I illustrates the second pressure therapy profile, in accordancewith another embodiment of the present specification;

FIG. 10J illustrates a plurality of cycles of the second pressuretherapy profile, in accordance with an embodiment of the presentspecification;

FIG. 10K illustrates a third pressure therapy profile, in accordancewith an embodiment of the present specification;

FIG. 10L illustrates a plurality of cycles of a pair of pressureprofiles, in accordance with an embodiment of the present specification;

FIG. 10M illustrates a plurality of cycles of a fourth pressure profile,in accordance with an embodiment of the present specification;

FIG. 10N illustrates a plurality of cycles of a fifth pressure profile,in accordance with an embodiment of the present specification;

FIG. 10O illustrates a plurality of cycles of a sixth pressure profile,in accordance with an embodiment of the present specification;

FIG. 10P illustrates a plurality of cycles of a seventh pressureprofile, in accordance with an embodiment of the present specification;

FIG. 11A illustrates a single lumen double balloon catheter comprisingan in-line heating element, in accordance with an embodiment of thepresent specification;

FIG. 11B illustrates a coaxial lumen double balloon catheter comprisingan in-line heating element, in accordance with an embodiment of thepresent specification;

FIG. 11C is a flow chart of a plurality of steps of using the catheterof FIG. 11A to perform ablation in a body lumen, such as Barrett'sesophagus of a patient, in accordance with an embodiment of the presentspecification;

FIG. 12A is an assembled schematic view of a vapor generation system, inaccordance with an embodiment of the present specification;

FIG. 12B is an exploded view of components upstream to an inductionheating unit of the vapor generation system of FIG. 12A;

FIG. 12C is an exploded view of components downstream to the inductionheating unit of the vapor generation system of FIG. 12A;

FIG. 13A illustrates a de-energized state of a 3-way flow controlsolenoid valve;

FIG. 13B illustrates an energized state of the 3-way flow controlsolenoid valve;

FIG. 14A shows a dual-balloon, multi-lumen catheter system, inaccordance with embodiments of the present specification;

FIG. 14B shows two elongate catheter shafts, in accordance withembodiments of the present specification;

FIG. 14C illustrates a first eyehole pattern, in accordance withembodiments of the present specification;

FIG. 14D illustrates a second eyehole pattern, in accordance withembodiments of the present specification;

FIG. 14E illustrates a transverse cross-sectional view of a multi-lumenshaft of the catheter system of FIG. 14A, in accordance with anembodiment of the present specification;

FIG. 15A shows a telescoping catheter handle with a first handlecomponent in a first position relative to a second handle component, inaccordance with embodiments of the present specification;

FIG. 15B shows the telescoping catheter handle with the first handlecomponent in a second position relative to the second handle component,in accordance with embodiments of the present specification;

FIG. 15C illustrates an induction heating unit attached in-series with aproximal end of the catheter handle, in accordance with embodiments ofthe present specification;

FIG. 15D shows a disassembled view of the second handle component of thecatheter handle, in accordance with embodiments of the presentspecification;

FIG. 15E shows a perspective view of the second handle componentseparated out from the first handle component of the catheter handle, inaccordance with embodiments of the present specification;

FIG. 15F shows a cross-sectional view of the second handle component ofthe catheter handle, in accordance with embodiments of the presentspecification;

FIG. 15G shows a break-away view of the first handle component of thecatheter handle, in accordance with embodiments of the presentspecification;

FIG. 15H is a cross-sectional view of the first handle component of thecatheter handle, in accordance with embodiments of the presentspecification;

FIG. 16A shows a single multi-lumen shaft, in accordance withembodiments of the present specification;

FIG. 16B illustrates a pattern of vapor exit ports on a portion of theshaft of FIG. 16A, in accordance with embodiments of the presentspecification;

FIG. 16C is a first cross-sectional view of the shaft of FIG. 16A, inaccordance with embodiments of the present specification;

FIG. 16D is a second cross-sectional view of the shaft of FIG. 16A, inaccordance with embodiments of the present specification;

FIG. 16E is a perspective view of a non-telescoping catheter handle, inaccordance with embodiments of the present specification;

FIG. 16F is a partial break-away view of the non-telescoping catheterhandle, in accordance with embodiments of the present specification;

FIG. 17A shows a clamp in accordance with embodiments of the presentspecification;

FIG. 17B shows the clamp removably attached to a shaft of an endoscope,in accordance with embodiments of the present specification;

FIG. 17C shows an induction heating unit mounted on an endoscopeseparately from a catheter handle (also mounted on the endoscope), inaccordance with embodiments of the present specification;

FIG. 17D illustrates an assembly of the induction heating unit beingslidably mounted to the clamp of FIG. 17A, in accordance with anembodiment of the present specification

FIG. 18 is an illustration of an embodiment of a disposable tubing setto be used with the ablation systems of the present specification;

FIG. 19 is an illustration of a telescoping catheter handle attached toan endoscope, in accordance with an embodiment of the presentspecification;

FIG. 20A is an assembled view of a vapor generator, in accordance withembodiments of the present specification;

FIG. 20B is a partial disassembled view of the vapor generator, inaccordance with embodiments of the present specification;

FIG. 20C is a disassembled view of a disposable pump of the vaporgenerator, in accordance with embodiments of the present specification;

FIG. 20D is an assembled view of the disposable pump, in accordance withembodiments of the present specification;

FIG. 20E shows the disposable pump fluidically connected to othercomponents of the vapor generator, in accordance with embodiments of thepresent specification;

FIG. 21 illustrates an ablation catheter placed in an uppergastrointestinal tract with Barrett's esophagus to selectively ablatethe Barrett's tissue, in accordance with an embodiment of the presentspecification;

FIG. 22 is a flowchart illustrating a method of ablation of Barrett'sesophagus in accordance with one embodiment of the presentspecification;

FIG. 23A illustrates deflated, lateral inflated, and frontal inflatedviews of an ablation catheter having an insulating membrane for duodenalablation, in accordance with one embodiment of the presentspecification;

FIG. 23B illustrates the ablation catheter of FIG. 44C deployed in aduodenum of a patient, in accordance with one embodiment of the presentspecification;

FIG. 24 is a flowchart illustrating a method of ablation of a colon inaccordance with one embodiment of the present specification;

FIG. 25 illustrates an upper gastrointestinal tract with a bleedingvascular lesion being treated by the ablation device, in accordance withan embodiment of the present specification;

FIG. 26 is a flowchart illustrating a method of ablation of an upper GItract in accordance with one embodiment of the present specification;

FIG. 27A is an illustration of pancreatic ablation being performed on apancreatic tumor in accordance with one embodiment of the presentspecification;

FIG. 27B is a flowchart listing the steps involved in one embodiment ofa method of pancreatic ablation;

FIG. 27C is a flowchart listing the steps involved in one embodiment ofa method of ablation of a pancreatic cyst;

FIG. 28 is a flowchart listing the steps involved in one embodiment of amethod of tissue ablation in a bile duct;

FIG. 29A is a flowchart illustrating a method of ablation ofbronchoalveolar tissue in accordance with an embodiment of the presentspecification;

FIG. 29B is a flowchart illustrating a method of ablation of bronchialtissue in accordance with another embodiment of the presentspecification;

FIG. 30A illustrates a cross-sectional view of a catheter for performingbronchial thermoplasty, in accordance with an embodiment of the presentspecification;

FIG. 30B illustrates a plurality of patterns of channels of a balloon ofthe catheter of FIG. 30A, in accordance with some embodiments of thepresent specification;

FIG. 30C illustrates a workflow for performing a bronchial thermoplastyprocedure using the catheter of FIG. 30A, in accordance with anembodiment of the present specification;

FIG. 31A illustrates a lung volume reduction (LVR) catheter, inaccordance with an embodiment of the present specification;

FIG. 31B illustrates the LVR catheter of FIG. 31A deployed through anendoscope/bronchoscope, in accordance with an embodiment of the presentspecification;

FIG. 31C is a workflow for performing lung volume reduction using thecatheter of FIG. 31A, in accordance with an embodiment of the presentspecification;

FIG. 32A illustrates a needle catheter incorporating one flexibleheating chamber of FIG. 1A through 1D, in accordance with an embodiment;

FIG. 32B illustrates the needle catheter of FIG. 32A incorporating twoflexible heating chambers, in accordance with an embodiment;

FIG. 32C is a flowchart illustrating one embodiment of a method ofablation of a tissue using the needle catheter of FIG. 32A;

DETAILED DESCRIPTION

Embodiments of the present specification provide ablation systems andmethods for treating various indications including, but not limited to,pre-cancerous or cancerous tissue in the esophagus, duodenum, bile duct,and pancreas. In various embodiments, steam, generated by heatingsaline, is used as an ablative agent. In various embodiments, theablation systems include a generator for generating an ablative agent(steam generator), comprising a source for providing a fluid (saline)for conversion to a vapor (steam) and a catheter for converting anddelivering said steam, wherein the catheter comprises at least oneelectrode embedded in a central lumen of the catheter and configured tofunction as a heating chamber to convert the saline to steam. Theablation systems further include an attachment at a distal end of thecatheter, wherein the attachment comprises at least one of a needle,cap, hood, or disc. The attachment is configured to direct the deliveryof ablative agent. The catheters may further include positioningelements to position the catheter for optimal steam delivery. Theattachments and positioning elements are configured to create seals andform enclosed treatment volumes for the delivery of steam and ablationof target tissues. In embodiments, the ablation systems and methods ofthe present specification are configured to enclose an area or volume oftissue with at least one positioning attachment, fill that area orvolume with vapor, allow the temperature in the area or volume to riseabove 100° C., and then let the additional vapor escape, maintaining thetemperature above 100° C. for a predetermined duration of time and thepressure in the area or volume less than 5 atm to allow the vapor tocondense and ablate the tissue.

Configurations for the various catheters of the ablation systems of theembodiments of the present specification may be different based on thetissue or organ systems being treated. For example, in some embodiments,catheters for esophageal and duodenal ablation are similar, with theexception that the spacing between two positioning elements, positionedat distal and proximal ends of a distal portion of the catheter withvapor delivery ports between the two positioning elements, may begreater for esophageal applications (approximately 1-20 cm) than forduodenal applications (approximately 1-10 cm). Distribution and depth ofablation provided by the systems and methods of the presentspecification are dependent on the duration of exposure to steam, theablation size, the temperature of the steam, the contact time with thesteam, and the tissue type.

In some embodiments, a patient is treated in a two-step process toensure complete or near complete ablation of a target tissue. In someembodiments, a patient is first treated with a catheter having twopositioning elements—a distal positioning element that is initiallydeployed followed by a proximal positioning element deployed thereafter,and a tube length with ports positioned between the two positioningelements, thereby enabling wide area circumferential ablation. Thepositioning elements may be a balloon, a disc, or any other structure. Afirst seal is created by contact of the periphery of the positioningelements with a patient's tissue at said distal and proximal positioningelements. Creation of the first seal results in the formation of anenclosed first treatment volume, bounded by the distal positioningelement at the distal end, the proximal positioning element as theproximal end, and the walls of the patient's tissue, such as theesophagus or duodenum, on the sides. Ablative energy, in the form ofsteam, is then delivered by the catheter via the ports into the firsttreatment volume, where it condenses and contacts the patient's tissuefor circumferential ablation and cannot escape from the distal orproximal ends as it is blocked by the positioning elements or,alternatively, controllably escapes from the distal or proximal endsbased on the configuration of the positioning elements, as furtherdescribed below.

After ablation is performed using the catheter with two positioningelements, the ablation area is examined by the physician. Upon observingthe patient, the physician may identify patches of tissue requiringfocused ablation. A second step is then performed, wherein a secondcatheter with a needle or cap, hood, or disc attachment on the distalend is passed through an endoscope and used for focal ablation. Theneedle provides for directed, focal ablation and the cap, hood, or discattachment encloses the focal ablation area, creating a second seal andan enclosed second treatment volume for ablation of the tissue. The sealis created by positioning at least a portion of a periphery of the cap,hood, or disc attachment in contact with a surface of a patient'stissue, such as the esophagus or duodenum, such that a portion of thepatient's tissue is positioned within an area circumscribed by theattachment. A second treatment volume, configured to receive steam andbounded by the sides of the attachment and said circumscribed portion ofpatient tissue, is created when the seal is formed. Ablative energy, inthe form of steam, is then delivered via the catheter by at least oneport at the distal tip of the catheter into the second treatment volume,where it condenses and contacts the patient's tissue for focal ablationand cannot escape as it is bounded by the attachment or, alternatively,controllably escapes from the attachment based on the configuration ofthe attachment, as further described below. In one embodiment, the flowrate of vapor out of the enclosed, or partially enclosed, volume is apredefined percentage of the flow rate of vapor into the enclosed, orpartially enclosed, volume from the catheter ports, where the predefinedpercentage is in a range of 1% to 80%, preferably less than 50%, andmore preferably less than 30%. The at least one port is positioned at adistal end of the catheter such that it exits into the second treatmentvolume when the attachment is positioned.

During both the first and second steps, when creating the enclosed firstand second treatment volumes, it is preferred to avoid creating aperfect (100%) seal. A perfect seal would trap air in the treatmentvolume. The trapped air would not be hot, relative to the steam used forablation, and, therefore, would create ‘cold air pockets’ which act as aheat sink, sapping a portion of the thermal ablation energy of the steamand resulting in uneven distribution of the ablative energy of thesteam. Creating less than a perfect seal allows for the air to be pushedout of the treatment volume, through a gap in the seal, as steam isdelivered into the treatment volume.

Additionally, as the temperature in the treatment volume increases, nosteam escapes until the temperature is greater than or equal to 100° C.,at which point steam condensation stops and the steam is allowed toescape through the gap, preventing excessive pressurization of thetreatment volume. In some embodiments, the catheter includes a filterwith micro-pores which provides back pressure to the delivered steam,thereby pressurizing the steam as it enters the treatment volume fromthe catheter. The predetermined size of micro-pores in the filterdetermine the backpressure and hence the temperature of the steam beinggenerated. During ablation with the attachment with two positioningelements, in various embodiments, a gap, or less than perfect seal, ispositioned only at the distal positioning element, only at the proximalpositioning element, or at both the distal and proximal positioningelements.

To create the gaps or less than perfect seals and allow air to leak orbe pushed out of the treatment volumes, embodiments of the presentspecification provide positioning elements or attachments that have arange of 40% to 99% of their surface area in contact with the patienttissue. In embodiments, a surface area of a cross-sectional slice alonga plane where a positioning element or attachment contacts the tissue isin a range of 20% to 99%. A low value, such as of 20%, represents anextremely porous seal, indicates that spacing exists between thepositioning element or attachment and the tissue or that the positioningelement or attachment includes voids therein, while a high value, suchas 99%, represents a near perfect seal. Additionally, the first andsecond seals are considered low pressure seals, wherein pressure withinthe first and second treatment volumes formed by the seals is less than5 atm and usually close to 1 atm. Therefore, as the pressure rises abovea predetermined pressure level, the seal breaks and the heated air orvapor is allowed to escape, thereby obviating the need for a pressuresensor in the catheter itself.

In embodiments, one or more of the positioning elements or attachmentsare configured such that they permit a range of flow out of thetreatment volumes enclosed by the two positioning elements orattachment. The permissible flow out is a function of steam flow intothe enclosed volume, thereby acting as a relief valve and allowing forthe maintenance of a desired pressure range (less than 5 atm) withoutregulation from the steam generator itself. In some embodiments, thepositioning element or attachment comprises a plurality of spaces withinthe surface area of the positioning element or attachment and/or betweenthe periphery of the positioning element or attachment and the tissuesufficient to permit a flow of fluid out of the enclosed volume in arange of 1 to 80% of the steam input flowrate to maintain the pressurelevel within the enclosed volume at less than 5 atm without regulationfrom the steam generator.

In some embodiments, the enclosed volume ranges from 3 cubic centimeters(cc) to 450 cc, when a surface area of mucosa to be ablated ranges from5 square centimeter (cm²) to 200 cm².

In embodiments, one or more of the positioning elements or attachmentare deformable over the course of treatment. Positioning elements andattachments in accordance with the embodiments of the presentspecification are designed to physically modify or deform when apressure in the treatment volume increases above 10% of a baselinepressure, therefore effectively acting as a pressure relief valve. As aresult of the ability to deform, the flow out of the volume enclosed bythe two positioning elements or attachment is variable. In an exemplaryembodiment, only a small portion, if any, of flow out of the enclosedvolume is blocked at the beginning of therapy. The percentage of flowthat is blocked decreases over the course of the therapy, therebyincreasing leakiness, due to pressure changes. In some embodiments,assuming a positioning element or attachment blocks flow out of anenclosed volume (or has the cross-sectional area covered) in a range of100% (total flow blockage or total cross section covered) to 20% (only20% of flow blocked or only 20% of cross sectional area covered) at thestart of treatment, the percentage changes during treatment where theamount of blockage/cross sectional area is decreased by 1% to 25%relative to the starting percentage. In various embodiments, aspreviously stated, it is preferred that pressure sensors are notincluded in the catheter itself to reduce costs and possible sensorfailure. Therefore, the deformable positioning elements naturally act asrelief valves, without requiring active pressure sensing.

In various embodiments, the ablation devices and catheters described inthe present specification are used in conjunction with any one or moreof the heating systems described in U.S. patent application Ser. No.14/594,444, entitled “Method and Apparatus for Tissue Ablation”, filedon Jan. 12, 2015 and issued as U.S. Pat. No. 9,561,068 on Feb. 7, 2017,which is herein incorporated by reference in its entirety.

“Treat,” “treatment,” and variations thereof refer to any reduction inthe extent, frequency, or severity of one or more symptoms or signsassociated with a condition.

“Duration” and variations thereof refer to the time course of aprescribed treatment, from initiation to conclusion, whether thetreatment is concluded because the condition is resolved or thetreatment is suspended for any reason. Over the duration of treatment, aplurality of treatment periods may be prescribed during which one ormore prescribed stimuli are administered to the subject.

“Period” refers to the time over which a “dose” of stimulation isadministered to a subject as part of the prescribed treatment plan.

The term “and/or” means one or all of the listed elements or acombination of any two or more of the listed elements.

In the description and claims of the application, each of the words“comprise” “include” and “have”, and forms thereof, are not necessarilylimited to members in a list with which the words may be associated. Theterms “comprises” and variations thereof do not have a limiting meaningwhere these terms appear in the description and claims.

Unless otherwise specified, “a,” “an,” “the,” “one or more,” and “atleast one” are used interchangeably and mean one or more than one.

The term “controller” refers to an integrated hardware and softwaresystem defined by a plurality of processing elements, such as integratedcircuits, application specific integrated circuits, and/or fieldprogrammable gate arrays, in data communication with memory elements,such as random access memory or read only memory where one or moreprocessing elements are configured to execute programmatic instructionsstored in one or more memory elements.

The term “vapor generation system” refers to any or all of the heater orinduction-based approaches to generating steam from water described inthis application.

For any method disclosed herein that includes discrete steps, the stepsmay be conducted in any feasible order. And, as appropriate, anycombination of two or more steps may be conducted simultaneously.

Also herein, the recitations of numerical ranges by endpoints includeall numbers subsumed within that range (e.g., 1 to 5 includes 1, 1.5, 2,2.75, 3, 3.80, 4, 5, etc.). Unless otherwise indicated, all numbersexpressing quantities of components, molecular weights, and so forthused in the specification and claims are to be understood as beingmodified in all instances by the term “about.” Accordingly, unlessotherwise indicated to the contrary, the numerical parameters set forthin the specification and claims are approximations that may varydepending upon the desired properties sought to be obtained by thepresent specification. At the very least, and not as an attempt to limitthe doctrine of equivalents to the scope of the claims, each numericalparameter should at least be construed in light of the number ofreported significant digits and by applying ordinary roundingtechniques.

Notwithstanding that the numerical ranges and parameters setting forththe broad scope of the specification are approximations, the numericalvalues set forth in the specific examples are reported as precisely aspossible. All numerical values, however, inherently contain a rangenecessarily resulting from the standard deviation found in theirrespective testing measurements.

The devices and methods of the present specification can be used tocause controlled focal or circumferential ablation of targeted tissue tovarying depth in a manner in which complete healing withre-epithelialization can occur. Additionally, the vapor could be used totreat/ablate benign and malignant tissue growths resulting indestruction, liquefaction and absorption of the ablated tissue. The doseand manner of treatment can be adjusted based on the type of tissue andthe depth of ablation needed. The ablation device can be used not onlyfor the treatment of cardiac arrhythmias, Barrett's esophagus andesophageal dysplasia, flat colon polyps, gastrointestinal bleedinglesions, endometrial ablation, pulmonary ablation, but also for thetreatment of any mucosal, submucosal or circumferential lesion, such asinflammatory lesions, tumors, polyps and vascular lesions. The ablationdevice can also be used for the treatment of focal or circumferentialmucosal or submucosal lesions of any hollow organ or hollow body passagein the body. The hollow organ can be one of gastrointestinal tract,pancreaticobiliary tract, genitourinary tract, respiratory tract or avascular structure such as blood vessels. The ablation device can beplaced endoscopically, radiologically, surgically or under directvisualization. In various embodiments, wireless endoscopes or singlefiber endoscopes can be incorporated as a part of the device. In anotherembodiment, magnetic or stereotactic navigation can be used to navigatethe catheter to the desired location. Radio-opaque or sonolucentmaterial can be incorporated into the body of the catheter forradiological localization. Ferro- or ferromagnetic materials can beincorporated into the catheter to help with magnetic navigation.

Ablative agents such as steam, heated gas or cryogens, such as, but notlimited to, liquid nitrogen are inexpensive and readily available andare directed via the infusion port onto the tissue, held at a fixed andconsistent distance, targeted for ablation. This allows for uniformdistribution of the ablative agent on the targeted tissue. The flow ofthe ablative agent is controlled by a microprocessor according to apredetermined method based on the characteristic of the tissue to beablated, required depth of ablation, and distance of the port from thetissue. The microprocessor may use temperature, pressure or othersensing data to control the flow of the ablative agent. In addition, oneor more suction ports are provided to suction the ablation agent fromthe vicinity of the targeted tissue. The targeted segment can be treatedby a continuous infusion of the ablative agent or via cycles of infusionand removal of the ablative agent as determined and controlled by themicroprocessor.

It should be appreciated that the devices and embodiments describedherein are implemented in concert with a controller that comprises amicroprocessor executing control instructions. The controller can be inthe form of any computing device, including desktop, laptop, and mobiledevice, and can communicate control signals to the ablation devices inwired or wireless form.

The present invention is directed towards multiple embodiments. Thefollowing disclosure is provided in order to enable a person havingordinary skill in the art to practice the invention. Language used inthis specification should not be interpreted as a general disavowal ofany one specific embodiment or used to limit the claims beyond themeaning of the terms used therein. The general principles defined hereinmay be applied to other embodiments and applications without departingfrom the spirit and scope of the invention. Also, the terminology andphraseology used is for the purpose of describing exemplary embodimentsand should not be considered limiting. Thus, the present invention is tobe accorded the widest scope encompassing numerous alternatives,modifications and equivalents consistent with the principles andfeatures disclosed. For purpose of clarity, details relating totechnical material that is known in the technical fields related to theinvention have not been described in detail so as not to unnecessarilyobscure the present invention.

It should be noted herein that any feature or component described inassociation with a specific embodiment may be used and implemented withany other embodiment unless clearly indicated otherwise.

FIG. 1A illustrates an ablation system 100, in accordance withembodiments of the present specification. The ablation system comprisesa catheter 10 having at least one first distal attachment or positioningelement 11 and an internal heating chamber 18, disposed within a lumenof the catheter 10 and configured to heat a fluid provided to thecatheter 10 to change said fluid to a vapor for ablation therapy. Insome embodiments, the catheter 10 is made of or covered with aninsulated material to prevent the escape of ablative energy from thecatheter body. The catheter 10 comprises one or more infusion ports 12for the infusion of ablative agent, such as steam. In some embodiments,the one or more infusion ports 12 comprises a single infusion port atthe distal end of a needle. In some embodiments, the catheter includes asecond positioning element 13 proximal to the infusion ports 12. Invarious embodiments, the first distal attachment or positioning element11 and second positioning element 13 may be any one of a disc, hood,cap, or inflatable balloon. In some embodiments, the first distalattachment or positioning element 11 and second positioning element 13include pores 19 for the escape of air or ablative agent. A fluid, suchas saline, is stored in a reservoir, such as a saline pump 14, connectedto the catheter 10. Delivery of the ablative agent is controlled by acontroller 15 and treatment is controlled by a treating physician viathe controller 15. The controller 15 includes at least one processor 23in data communication with the saline pump 14 and a catheter connectionport 21 in fluid communication with the saline pump 14. In someembodiments, at least one optional sensor 17 monitors changes in anablation area to guide flow of ablative agent. In some embodiments,optional sensor 17 comprises at least one of a temperature sensor orpressure sensor. In some embodiments, the catheter 10 includes a filter16 with micro-pores which provides back pressure to the delivered steam,thereby pressurizing the steam. The predetermined size of micro-pores inthe filter determine the backpressure and hence the temperature of thesteam being generated. In some embodiments, the system further comprisesa foot pedal 25 in data communication with the controller 15, a switch27 on the catheter 10, or a switch 29 on the controller 15, forcontrolling vapor flow.

In one embodiment, a user interface included with the microprocessor 15allows a physician to define device, organ, and condition which in turncreates default settings for temperature, cycling, volume (sounds), andstandard RF settings. In one embodiment, these defaults can be furthermodified by the physician. The user interface also includes standarddisplays of all key variables, along with warnings if values exceed orgo below certain levels.

The ablation device also includes safety mechanisms to prevent usersfrom being burned while manipulating the catheter, including insulation,and optionally, cool air flush, cool water flush, and alarms/tones toindicate start and stop of treatment.

FIG. 1B is a transverse cross-section view 121 of a flexible heatingchamber 130 configured to be incorporated at or into a distal portion ortip of a catheter, in accordance with an embodiment of the presentspecification. FIG. 1C illustrates a transverse cross-section view 122 aand a longitudinal cross-section view 122 b of a first array ofelectrodes 136 along with a transverse cross-section view 123 a and alongitudinal cross-section view 123 b of a second array of electrodes138 of a flexible heating chamber for a catheter, in accordance with anembodiment of the present specification. FIGS. 1D and 1E are,respectively, transverse and longitudinal cross-section views 124, 125of the heating chamber 130 including assembled first and secondelectrodes 136, 138.

Referring now to FIGS. 1B, 1C, 1E, and 1E simultaneously, the heatingchamber 130 comprises an outer covering 132 and a coaxial inner core,channel, or lumen 134. A plurality of electrodes, configured as firstand second arrays of electrodes 136, 138, is disposed between the outercovering 132 and the inner lumen 134. In some embodiments, the first andsecond array of electrodes 136, 138 respectively comprise metal rings142, 144 from which a plurality of electrode fins or elements 136′, 138′extend radially into the space between the outer covering 132 and innerlumen 134 (see 122 a, 123 a). The electrode fins or elements 136′, 138′also extend longitudinally along a longitudinal axis 150 of the heatingchamber 130 (see 122 b, 123 b). In other words, each of the electrodefins 136′, 138′ have a first dimension along a radius of the heatingchamber 130 and a second dimension along a longitudinal axis 150 of theheating chamber 130. The electrode fins or elements 136′, 138′ define aplurality of segmental spaces 140 there-between through whichsaline/water flows and is vaporized into steam. Electrical current isdirected from the controller, into the catheter, through a lumen, and tothe electrodes 136, 138 which causes the fins or elements 136′, 138′ togenerate heat which is then transferred to the saline in order toconvert the saline to steam. The first and second dimensions enable theelectrodes 136, 138 to have increased surface area for heating thesaline/water flowing in the spaces 140. In accordance with anembodiment, the first electrodes 136 have a first polarity and thesecond electrodes 138 have a second polarity opposite said firstpolarity. In an embodiment, the first polarity is negative (cathode)while the second polarity is positive (anode).

In embodiments, the outer covering 132 and the inner lumen 134 arecomprised of silicone, Teflon, ceramic or any other suitablethermoplastic elastomer known to those of ordinary skill in the art. Theinner lumen 134, outer covering 132, electrodes 136, 138 (includingrings 142, 144 and fins or elements 136′, 138′) are all flexible toallow for bending of the distal portion or tip of the catheter toprovide better positioning of the catheter during ablation procedures.In embodiments, the inner lumen 134 stabilizes the electrodes 136, 138and maintains the separation or spacing 140 between the electrodes 136,138 while the tip of the catheter flexes or bends during use.

As shown in FIGS. 1D and 1E, when the heating chamber 130 is assembled,the electrode fins or elements 136′, 138′ interdigitate or interlockwith each other (similar to fingers of two clasped hands) such that acathode element is followed by an anode element which in turn isfollowed by a cathode element that is again followed by an anode elementand so on, with a space 140 separating each cathode and anode element.In various embodiments, each space 140 has a distance from a cathodeelement to an anode element ranging from 0.01 mm to 2 mm. In someembodiments, the first array of electrodes 136 has a range of 1 to 50electrode fins 136′, with a preferred number of 4 electrode fins 136′,while the second array of electrodes 138 has a range of 1 to 50electrode fins 138′, with a preferred number of 4 electrode fins 138′.In various embodiments, the heating chamber 130 has a width w in a rangeof 1 to 5 mm and a length/in a range of 5 to 50 mm.

In accordance with an aspect of the present specification, multipleheating chambers 130 can be arranged in the catheter tip. FIGS. 1F and1G are longitudinal cross-section views of a catheter tip 155 whereintwo heating chambers 130 are arranged in series, in accordance with anembodiment of the present specification. Referring to FIGS. 1F and 1G,the two heating chambers 130 are arranged in series such that a space160 between the two heating chambers 130 acts as a hinge to impart addedflexibility to the catheter tip 155 to allow it to bend. The two heatingchambers 130 respectively comprise interdigitated first and secondarrays of electrodes 136, 138. Use of multiple, such as two, heatingchambers 130 enables a further increase in the surface area of theelectrodes 136, 138 while maintaining flexibility of the catheter tip155.

Referring now to FIGS. 1B through 1G, for generating steam, fluid isdelivered from a reservoir, such as a syringe, to the heating chamber130 by a pump or any other pressurization means. In embodiments, thefluid is sterile saline or water that is delivered at a constant orvariable fluid flow rate. An RF generator, connected to the heatingchamber 130, provides power to the first and second arrays of electrodes136, 138. As shown in FIG. 1E, during vapor generation, as the fluidflows through spaces 140 in the heating chamber 130 and power is appliedto the electrodes 136, 138 causing the electrodes to heat, the fluid iswarmed in a first proximal region 170 of the heating chamber 130. Whenthe fluid is heated to a sufficient temperature, such as 100 degreesCentigrade at atmospheric pressure, the fluid begins to transform into avapor or steam in a second middle region 175. All of the fluid istransformed into vapor by the time it reaches a third distal region 180,after which it can exit a distal end 133 of the heating chamber 130 andexit the catheter tip 155. If the pressure in the heating chamber isgreater than atmospheric pressure, higher temperatures will be requiredand if it is lower than atmospheric pressure, lower temperatures willgenerate vapor.

In one embodiment, a sensor probe may be positioned at the distal end ofthe heating chambers within the catheter. During vapor generation, thesensor probe communicates a signal to the controller. The controller mayuse the signal to determine if the fluid has fully developed into vaporbefore exiting the distal end of the heating chamber. Sensing whetherthe saline has been fully converted into vapor may be particularlyuseful for many surgical applications, such as in the ablation ofvarious tissues, where delivering high quality (low water content) steamresults in more effective treatment. In some embodiments, the heatingchamber includes at least one sensor 137. In various embodiments, saidat least one sensor 137 comprises an impedance, temperature, pressure orflow sensor, with the pressure sensor being less preferred. In oneembodiment, the electrical impedance of the electrode arrays 136, 138can be sensed. In other embodiments, the temperature of the fluid,temperature of the electrode arrays, fluid flow rate, pressure, orsimilar parameters can be sensed.

FIG. 1H and FIG. 1I illustrate multiple lumen balloon catheters 161 and171 respectively, in accordance with embodiments of the presentspecification. The catheters 161, 171 each include an elongate body 162,172 with a proximal end and a distal end. The catheters 161, 171 includeat least one positioning element proximate their distal ends. In variousembodiments, the positioning element is a balloon. In some embodiments,the catheters include more than one positioning element.

In the embodiments depicted in FIGS. 1H and 1I, the catheters 161, 171each include a proximal balloon 166, 176 and a distal balloon 168, 178positioned proximate the distal end of the body 162, 172 with aplurality of infusion ports 167, 177 located on the body 162, 172between the two balloons 166, 176, and 168, 178. The body 162, 172 alsoincludes at least one heating chamber 130 proximate and just proximal tothe proximal balloon 166, 176. The embodiment of FIG. 1H illustrates oneheating chamber 130 included in the body 165 proximate and just proximalto the proximal balloon 166. In some embodiments, multiple heatingchambers are arranged in series in the body of the catheter.

In the embodiment of FIG. 1I, two heating chambers 130 are arranged inthe body 172 proximate and just proximal to the proximal balloon 176.Referring to FIG. 1I, for inflating the balloons 176, 178 and providingelectrical current and liquid to the catheter 171, a fluid pump 179, anair pump 173 and an RF generator 184 are coupled to the proximal end ofthe body 172. The air pump 173 pumps air via a first port through afirst lumen (extending along a length of the body 172) to inflate theballoons 176, 178 so that the catheter 171 is held in position for anablation treatment. In another embodiment, the catheter 171 includes anadditional air port and an additional air lumen so that the balloons176, 178 may be inflated individually. The fluid pump 179 pumps thefluid through a second lumen (extending along the length of the body172) to the heating chambers 130. The RF generator 184 supplieselectrical current to the electrodes 136, 138 (FIGS. 1G, 1H), causingthe electrodes 136, 138 to generate heat and thereby converting thefluid flowing through the heating chambers 130 into vapor. The generatedvapor flows through the second lumen and exits the ports 177. Theflexible heating chambers 130 impart improved flexibility andmaneuverability to the catheters 161, 171, allowing a physician tobetter position the catheters 161, 171 when performing ablationprocedures, such as ablating Barrett's esophagus tissue in an esophagusof a patient.

FIG. 1J is a flow chart of a plurality of steps of using the catheters161, 171 of FIG. 1H or 1I to perform ablation of Barrett's esophagustissue in an esophagus of a patient, in accordance with embodiments ofthe present specification. At step 185, insert the catheter 161, 171into an esophagus of a patient. At step 186, position the distal balloon168, 178 distal to a portion of Barrett's esophagus and the proximalballoon 166, 176 proximal to a portion of Barrett's esophagus such thatinfusion ports 167, 177 are positioned in said portion of Barrett'sesophagus. At step 187, inflate the balloons 166, 176 and 168, 178 usingan air pump to position the catheter 161, 171 in the esophagus. At step188, provide fluid, such as water or saline, to the catheter 161, 171via a fluid pump. Finally, at step 189, provide electrical current toelectrodes 136, 138 using an RF generator to heat the electrodes andconvert the fluid to vapor, wherein the generated vapor is deliveredthrough the infusion ports 167, 177 to ablate the Barrett's esophagustissue of the patient.

FIG. 1K illustrates a catheter 191 with proximal and distal positioningelements 196, 198 and an electrode heating chamber 130, in accordancewith embodiments of the present specification. The catheter 191 includesan elongate body 192 with a proximal end and a distal end. The catheter191 includes a proximal positioning element 196 and a distal positioningelement 198 positioned proximate the distal end of the body 192 with aplurality of infusion ports 197 located on the body 192 between the twopositioning elements 196, 198. The body 192 also includes at least oneheating chamber 130 within a central lumen. In some embodiments, theproximal positioning element 196 and distal positioning element 198comprises compressible discs which expand on deployment. In someembodiments, the proximal positioning element 196 and distal positioningelement 198 are comprised of a shape memory metal and are transformablefrom a first, compressed configuration for delivery through a lumen ofan endoscope and a second, expanded configuration for treatment. Inembodiments, the discs include a plurality of pores 199 to allow for theescape of air at the start of an ablation procedure and for the escapeof steam once the pressure and/or temperature within an enclosedtreatment volume created between the two positioning elements 196, 198reaches a predefined limit, as described above. In some embodiments, thecatheter 191 includes a filter 193 with micro-pores which provides backpressure to the delivered steam, thereby pressurizing the steam. Thepredetermined size of micro-pores in the filter determine thebackpressure and hence the temperature of the steam being generated.

It should be appreciated that the filter 193 may be any structure thatpermits the flow of vapor out of a port and restricts the flow of vaporback into, or upstream within, the catheter. Preferably, the filter is athin porous metal or plastic structure, positioned in the catheter lumenand proximate one or more ports. Alternatively, a one-way valve may beused which permits vapor to flow out of a port but not back into thecatheter. In one embodiment, this structure 193, which may be a filter,valve or porous structure, is positioned within 5 cm of a port,preferably in a range of 0.1 cm to 5 cm from a port, and more preferablywithin less than 1 cm from the port, which is defined as the actualopening through which vapor may flow out of the catheter and into thepatient.

FIG. 1L is a flow chart illustrating a method of ablating a tissueinside a gastrointestinal tract of a patient, in accordance with someembodiments of the present specification. In embodiments, the method ofFIG. 1L illustrates circumferential vapor ablation that is followed by afocused vapor ablation after observing the patient, to treat apre-cancerous tissue, cancerous tissue, or otherwise unwanted tissue inthe esophagus, duodenum, bile duct, or pancreas. In embodiments,ablation catheters disclosed in the present specification, such asablation catheter 191 of FIG. 1K, are used to perform the ablationmethod of FIG. 1L.

At 102, an ablation catheter configured for the gastrointestinal (GI)tract is inserted into the GI tract of the patient. At 104, a seal iscreated between an exterior surface of the ablation catheter and aninterior wall of the GI tract, forming a treatment volume. The seal iscreated by the expansion of one or more positioning elements of theablation catheter, as explained in the embodiments of the presentspecification. In some embodiments, the seal is temperature dependentand it breaks or becomes porous when the temperature or pressure withinthe sealed portion or treatment volume exceeds a threshold value. In oneembodiment, the specific temperature is 90° C. In some embodiments, theseal is pressure dependent and it begins to leak when the pressurewithin the sealed portion or treatment volume exceeds a specificpressure. In one embodiment, the specific pressure is 5 atm. At 106,vapor is delivered through the ablation catheter into the sealed portionwithin the GI tract, while the seal is still in place. At 108, the vaporcondenses on the tissue under treatment, thereby ablating the tissue.

FIG. 1M is a flow chart illustrating a method of ablating a tissueinside a gastrointestinal tract of a patient, in accordance with otherembodiments of the present specification. In embodiments, the method ofFIG. 1M illustrates circumferential vapor ablation that is followed byfocused vapor ablation after observing the patient, to treat apre-cancerous tissue, cancerous tissue, or otherwise unwanted tissue inthe esophagus, duodenum, bile duct, or pancreas. In embodiments,ablation catheters disclosed in the present specification, such asablation catheter 191 of FIG. 1K, are used to perform the ablationmethod of FIG. 1M. At 112, an ablation catheter configured for thegastrointestinal (GI) tract is inserted into the GI tract of thepatient. At 114, saline with a variable flow rate is introduced throughthe ablation catheter into the GI tract. At 116, the saline is heatedusing RF energy to generate vapor through the ablation catheter into theGI tract. In embodiments, the rate of flow of the saline during vapordelivery is different from flow of the saline during the phase where notherapy is delivered. In some embodiments, the rate of flow of salineduring the therapy is lower than that during no therapy. In someembodiments, the rate of flow of saline during the therapy is lower thanthat during no therapy. At 118, the vapor condenses on the tissue undertreatment, thereby ablating the tissue.

Exemplary Treatment—Gastrointestinal System

FIG. 1N is a flow chart illustrating a method for treating agastrointestinal condition in a patient using a vapor ablation system,in accordance with embodiments of the present specification. In variousembodiments, the condition may include, but is not limited to, obesity,excess weight, eating disorders, metabolic syndrome, and diabetes, fattyliver, non-alcoholic fatty liver disease (NAFLD), or non-alcoholicsteatohepatitis (NASH). The vapor ablation system comprises a controllerhaving at least one processor in data communication with at least onepump and a catheter connection port in fluid communication with the atleast one pump. At step 101, a proximal end of a first catheter isconnected to the catheter connection port to place the first catheter influid communication with the at least one pump. The first cathetercomprises at least two positioning elements separated along a length ofthe catheter and at least two ports positioned between the at least twopositioning elements, wherein each of the at least two positioningelements has a first configuration and a second configuration, andwherein, in the first configuration, each of the at least twopositioning elements is compressed within the catheter and in the secondconfiguration, each of the at least two positioning elements is expandedto be at least partially outside the catheter. At step 103, the firstcatheter is positioned inside a patient such that, upon being expandedinto the second configuration, a distal one of the at least twopositioning elements is positioned within in the patient's smallintestine and a proximal one of the at least two positioning elements isproximally positioned more than 1 cm from the distal one of the at leasttwo positioning elements. Then, at step 105 each of the at least twopositioning elements is expanded into their second configurations. Atstep 107, the controller is activated, wherein, upon activation, thecontroller is configured to cause the at least one pump to deliversaline into at least one lumen in the first catheter and, wherein, uponactivation, the controller is configured to cause an electrical currentto be delivered to at least one electrode positioned within the at leastone lumen of the first catheter. The electrical current causes theelectrode to heat and contact of the saline with the heating electrodeconverts the saline to steam which is delivered via the at least twoports to ablate gastrointestinal tissue. In various embodiments, eachtreatment dose delivered to the gastrointestinal tract comprises thefollowing parameters: 1-15 cm of contiguous or non-contiguous smallintestine mucosa is treated; at least 50% of a circumference of a smallintestine is treated; energy in a range of 5-25 J/cm²; delivery periodof 1-60 seconds; delivery rate of 5-2,500 cal/sec; total dose of 5-40cal/gm of tissue to be ablated; target tissue temperature between 60° C.and 110° C.; vapor temperature between 99° C. and 110° C.; and pressurein the gastrointestinal tract less than 5 atm, and preferably less than1 atm.

At step 109, the controller shuts off the delivery of saline andelectrical current after a time period ranging from 1 to 60 seconds. Inembodiments, the controller automatically shuts off the delivery ofsaline and electrical current. The controller is repeatedly activated atstep 111 to deliver saline into the lumen and electrical current to theat least one electrode until the physician terminates the procedure. Insome embodiments, the system further comprises a foot pedal in datacommunication with the controller, a switch on the catheter, or a switchon the controller, for controlling vapor flow and step 111 is achievedusing the foot pedal in data communication with the controller, a switchon the catheter, or a switch on the controller. The first catheter isremoved from the patient at step 113.

The physician then waits for at least at least six weeks at step 115before evaluating the efficacy of treatment. In some embodiments, thephysician waits a time frame ranging from six weeks to two years beforeevaluating efficacy of treatment. An efficacy of the treatment isdetermined at step 117 my measuring at least one physiological parameterrelating to the gastrointestinal disorder, as disclosed in the presentspecification, and comparing the measured parameter to a desiredtherapeutic endpoint. If the therapeutic endpoint has been achieved,treatment is complete at step 129. If the therapeutic endpoint has notbeen achieved, ablation therapy is repeated at step 119.

It should be appreciated that, while the above discussion is directed toduodenal ablation, any ablation catheter or system of the presentspecification, used to ablate tissue in an organ, may be used with acontroller, wherein the controller is configured to limit a pressuregenerated by ablation fluid, such as steam/vapor, within the organ toless than 5 atm or 100 psi. In various embodiments, the organ may be apancreatic cyst, esophagus, duodenum/small bowel, uterine cavity,prostate, bronchus or alveolar space.

Needle Vapor Delivery Device

FIG. 2A shows perspective views of a needle-based vapor delivery device2000, in accordance with an embodiment of the present specification. Thedevice 2000 comprises a needle 2005 protruding from a distal end 2011 ofa composite handle 2010. The needle 2005 has a needle tip portion 2001and is encompassed at its proximal end by an inner or middle catheter2002 and an outer catheter 2003. In some embodiments, the compositehandle 2010 and the needle 2005 are hollow. In some embodiments, theneedle 2005 is retractable within the composite handle 2010. In someembodiments, the needle 2005 is of stainless steel, the middle catheter2002 is of PTFE (Polytetrafluoroethylene) while the outer catheter 2003is of braided Teflon.

FIG. 2B is a cross-sectional view of the composite handle 2010illustrating the needle 2005 emanating from the distal end 2011, a frontor distal handle portion 2013 and a back or proximal handle portion2014. A lumen 2008 extends from a proximal end 2012 to the distal end2011 of the composite handle 2010 and is in fluid communication with alumen 2024 of the needle 2005. Saline enters the lumen 2008 from theproximal end 2012 and steam exits from at least one port 2007 located ata distal end 2006 of the needle 2005. A pressure sensor 2009 is locatedproximate the proximal end 2012 of the composite handle 2010.

FIG. 2C shows an enlarged view of the front or distal handle portion2013 of the composite handle 2010. Referring now to FIGS. 2B and 2C, thedistal handle portion 2013 is an assembly comprising a front tube 2015coupled, at its distal end, to a distal lock 2016 and, at its proximalend, to a front handle 2017. A lock 2021 secures the front tube 2015 tothe front handle 2017. A pressure sensor 2018 is located proximate aproximal end of the front handle 2017 while the pressure sensor 2009 islocated proximate the proximal end 2012.

FIG. 2D shows an enlarged view of the back or proximal handle portion2014 of the composite handle 2010. Referring now to FIGS. 2B, 2C and 2D,the proximal handle portion 2014 is an assembly comprising a back tube2019 coupled, at its distal end, to the front handle 2017 and, at itsproximal end, to a back handle 2020. A lock 2025 secures the back tube2019 to the back handle 2020. The lumen 2008 is covered or encompassedwithin a reinforce tube or sheath 2022. The proximal end 2012 of thecomposite handle 2010 includes a lure connection 2023 defining anopening to enable saline to enter the lumen 2008. The pressure sensor2009 is visible again in the enlarged view of the back or proximalhandle portion 2014 of FIG. 2D.

Referring again to FIGS. 2A, 2B, 2C and 2D, in accordance with anexemplary embodiment, the device 2000 has the following dimensions: alength of 1715 mm from a proximal end of the lure connection 2023 to thedistal end 2006 of the needle 2005, a length of 1367 mm from a distalend of the distal lock 2016 to the distal end 2006 of the needle 2005, alength of 41 mm from a proximal end of the distal lock 2016 to a distalend of the lock 2021, a length of 71 mm from the distal end of the lock2021 to a proximal end of the front handle 2017, a length of 83 mm fromthe proximal end of the front handle 2017 to a distal end of the lock2025, a length 124 mm from the distal end of the lock 2025 to theproximal end 2012, a length of 348 mm from the distal end of the distallock 2016 to the proximal end of the lure connection 2023, a length of62.8 mm from the proximal end of the distal lock 2016 to a proximal endof the front tube 2015, an outer diameter of 2.8 mm of the sheath 2022,an outer diameters of 19 mm of the front handle 2017 and the back handle2020, an inner diameters of 7.5 mm of the front and back tubes 2015,2019, and an outer diameters of 12.5 mm of the front and back tubes2015, 2019.

In accordance with an aspect of the present specification, the needlesof the needle ablation catheters and devices have a form factor thatenables the needle to be functional with a conventional endoscope—thatis, the form factor enables the needle to be slid through a workingchannel of the endoscope. FIGS. 3A and 3B illustrate a conventionalendoscope 3060 with a bending section 3062 and a needle 3005 of a needleablation catheter protruding from a working channel 3061 of theendoscope 3060. In embodiments, when bent, the bending section 3062 hasa curve length c₁ of 10 cm comprising a first distal length l₁ of 4 cm,a second middle length l₂ of 3 cm and a third proximal length l₃ of 3cm. When bent, a distance d1 between a distal end and a proximal end ofthe bending section 3062 is 5 cm. As shown in FIG. 3A, the needle 3005is capable of bending or flexing by at least an angle of 45 degrees.

FIGS. 4A, 4B show perspective views of a needle 4005 while FIG. 4Cillustrates cross-sectional views of the needle 4005, in accordance withan embodiment of the present specification. In accordance with anembodiment, the needle 4005 can be distinguished into the distal needletip portion 4001, a middle portion 4002′ and a proximal portion 4003′.FIGS. 4A, 4B and a longitudinal cross-sectional view 4030 of FIG. 4Cshow the needle tip portion 4001, the inner or middle catheter 4002 andthe outer catheter 4003. In accordance with an embodiment, the needletip portion 4001 has a length of 80 mm (+/−60 mm) from a proximal end toa distal end of the needle tip portion 4001. The needle 4005 has alength of 100 mm (+/−50 mm) from a proximal end of the middle portion4002′ to the distal end of the needle tip portion 4001. The proximalportion 4003′ has a length of 1650 mm.

Referring now to the longitudinal cross-sectional view 4030 of FIG. 4C,the middle portion 4002′ comprises a proximal laser cut portion 4026(also shown in FIG. 4B) and a distal tapered portion 4027. In accordancewith an embodiment of the present specification, the proximal portion4003′ houses or accommodates at least one flexible heating chamber 4028(comprising a plurality of RF electrodes) positioned proximate theproximal laser cut portion 4026 (the at least one flexible heatingchamber 4028 is also shown in FIG. 4B). During operation, saline entersfrom the proximal end (2012 of FIG. 2B) to reach the heating chamber4028 where the saline is converted to steam/vapor that exits through atleast one port 4007 located at the distal end 4006 of the needle 4005.

As shown in an enlarged cross-sectional view 4032, in one embodiment, ata proximal end of the tapered portion 4027—the needle 4005 has an innerdiameter of 1.76 mm and an outer diameter of 1.96 mm while the innercatheter 4002 has an outer diameter of 2.6 mm and an inner diameter of 2mm. In another embodiment, the inner catheter 4002 has an outer diameterof 2.7 mm and an inner diameter of 2.4 mm. At a distal end of thetapered portion 4027, the needle 4005 has an inner diameter of 0.9 mm.From the proximal end to the distal end, the portion 4027 has a taper orslope of 8.4 degrees with respect to a horizontal axis. The length ofthe tapered portion 4027 is 10 mm.

As shown in an enlarged cross-sectional view 4035, at the tip portion4001, the needle 4005 has an outer diameter of 1.1 mm and an innerdiameter of 0.9 mm. As shown in an enlarged cross-sectional view 4038,at the middle portion 4002′, the needle 4005 has an inner diameter of1.76 mm and an outer diameter of 1.96 mm while the inner or middlecatheter 4002 has an outer diameter of 2.6 mm. As shown in an enlargedcross-sectional view 4040, at the proximal portion 4003′, the needle4005 still has the inner diameter of 1.76 mm and the outer diameter of1.96 mm, the inner or middle catheter 4002 still has the outer diameterof 2.6 mm while the outer catheter 4003 has an inner diameter of 2.9 mmand an outer diameter of 3.3 mm.

In some embodiments, the proximal portion 4003′ of the needle 4005 hasan inner diameter of greater than or equal to 1.5 mm (to accommodate theheating chamber 4028) while the needle tip portion 4001 has an outerdiameter of less than or equal to 1.1 mm to minimize leaks andinfection. In some embodiments, the needle 4005 is electricallyinsulated and does not have leaks along its length (see FIG. 4D). Invarious embodiments, the needle 4005 is sufficiently stiff at the tipand proximal portions 4001, 4003′ and has a 10 to 20 cm flexible middleportion 4002′ in order to make a bend in the endoscope.

FIG. 4D illustrates cross-sectional views of the needle 4005, inaccordance with another embodiment of the present specification. In thisembodiment, the needle 4005 is covered or sheathed in an insulatingcoating 4042 that covers the proximal portion 4003′, the middle portion4002′ and the needle tip portion 4001 to a point proximate the at leastone port 4007. In some embodiments, the insulating coating 4042 coversthe entirety of the needle 4005, which, in some embodiments, comprisesthe distal 8 cm of the inner catheter. In some embodiments, needle 4005diameter is within a range of 12 Birmingham Gauge (G) and 30 G andneedle 4005 length is in a range of 1 cm to 10 cm. In some embodiments,the slope of the needle taper is defined in a range of 12 G/1 cm to 30G/10 cm. The proximal portion 4003′ houses or accommodates at least oneflexible heating chamber 4028 (comprising a plurality of electrodes)positioned proximate the proximal laser cut portion 4026.

Referring to FIG. 4D, in an embodiment, the needle 4005 has thefollowing dimensions: a length of 80 mm from the distal end 4006 of theneedle 4005 to the distal end of the middle portion 4002′, a length of 8mm from the distal end to the proximal end of the tapered portion 4027,a length of 1712 mm from the distal end of the laser cut portion 4026 toa proximal end of the proximal portion 4003′, a total length of 1800 mm(+/−30 mm) from the proximal end of the proximal portion 4003′ to thedistal end 4006 of the needle 4005, and the tapered portion 4027 has ataper or slope in a range of 1 to 20 degrees (or any increment therein),preferably a range of 3 to 10 degrees (or any increment therein), andmore preferably 6.2 degrees, with respect to a horizontal axis. At thetip portion 4001, the needle 4005 has an outer diameter of 1.1 mm and aninner diameter of 0.9 mm while at the proximal portion 4003′, the needle4005 has an inner diameter of 1.76 mm and an outer diameter of 1.96 mm.

FIG. 4E shows perspective views of various needles 4105, 4205, 4305illustrating the needle tip portions 4101, 4201, 4301 and insulatingcoatings 4102, 4202, 4302, in accordance with embodiments of the presentspecification. The needles 4105, 4205, 4305 are composed of metal suchas, but not limited to, stainless steel while the insulating coatings4102, 4202, 4302 comprise PTFE, ePTFE or silicone.

In accordance with an aspect of the present specification, the needlesof the needle ablation catheters are configured to have variablestiffness across their lengths. As shown in FIG. 5A, a proximal portion5003′ of a needle 5005 has a first stiffness, the middle portion 5002′has a second stiffness and a tip portion 5001 has a third stiffness. Insome embodiments, the second stiffness is less than the first stiffnessand the third stiffness. In some embodiments, the first and thirdstiffness are substantially same. In some embodiments, the firststiffness is greater than the third stiffness. In some embodiments, thefirst stiffness is less than the third stiffness.

Referring now to FIG. 4C in addition to FIGS. 5A and 5B, the middleportion 4002′, 5002′ includes the laser cut portion 4026 that impartsthe middle portion 4002′, 5002′ with the second stiffness therebyenabling the needle 4005, 5005 to bend at the portion 4002′, 5002′ yetthe comparatively higher first and third stiffness allows sufficientrigidity to the tip portion 4001, 5001 and the proximal portion 4003′,5003′. In some embodiments, the middle portion 4002′, 5002′ isconfigured to additionally include the tapered portion 4027. The taperedportion 4027 imparts further bendability and pliability to the middleportion 4002′, 5002′.

FIG. 5B illustrates various needles 5105, 5205, 5305 of needle ablationcatheters having variable stiffness, in accordance with some embodimentsof the present specification. Each needle 5105, 5205, 5305 has adifferent laser cut pattern in the middle portion 5102′, 5202′, 5302′,imparting each needle with a different stiffness in this portion andtherefore a different degree of flexibility. For example, in anembodiment, needle 5105 has a middle portion 5102′ laser cut such thatthe tip portion 5101 may be flexed in a range 5115 relative to theproximal portion 5103′. The variable stiffness allows for both bendingat the middle portion and pushability along the catheter body.

FIG. 5C illustrates laser cutting patterns or designs to impart variablelevels of stiffness to different portions of various needles 5405, 5505,in accordance with some embodiments of the present specification. Asshown in FIG. 5C, in one embodiment, the middle portion 5402′ of theneedle 5405 is configured to have a substantially helical or spirallaser cutting 5445. A pitch of the cutting 2045 varies along the lengthof the middle portion 5402′ to impart a predefined level of stiffness toenable the needle 5405 to bend along the middle portion 5402′. Inanother embodiment, a tip portion 5501 of a needle 5505 has a firstlaser cutting design 5546 imparting a first level of stiffness to theregion, the middle portion 5502′ has a second laser cutting design 5547imparting a second level of stiffness to the region and the proximalportion 5503′ has a third laser cutting design 5548 imparting a thirdlevel of stiffness to the region. In one embodiment, the first lasercutting design 5546 is such that less material of the needle 5505 in thetip portion 5501 is removed compared to the second laser cutting design5547. As a result the second level of stiffness is comparatively lessthan the first level of stiffness. On the other hand, the third lasercutting design 5548 may involve removal of no or substantially nomaterial in the proximal portion 5503′. Consequently, the third level ofstiffness is greater than the first and second level of stiffness.

FIG. 5D illustrates additional laser cutting designs to impart variablelevels of stiffness to different portions of various needles, inaccordance with some embodiments of the present specification. Thefigure illustrates first, second, third, fourth, fifth, sixth andseventh laser cutting patterns 5050, 5051, 5052, 5053, 5054, 5055, 5056,respectively. For example, the pattern 5056 is sparsest and thereforeimparts the least level of stiffness. Patterns 5052, 5054 and 5055 arecomparatively dense, in that they involve less removal of the materialof the needle, thereby corresponding to higher level of stiffnesscompared to the pattern 5056.

While in some embodiments, the needle 4005 houses the heating chamber4028—as shown in FIGS. 4C and 4D, in some embodiments the heatingchamber is housed in a separate vapor delivery catheter and not in theneedle. FIGS. 6A and 6B illustrate longitudinal cross-sectional views ofa vapor delivery catheter 605 having a handle 610 at a proximal end, anexpandable tip 615 at a distal tip and a lumen 620 extending from theproximal end to the distal end of the catheter 605. As shown in FIG. 6B,in some embodiments, the handle 610 is configured to lock onto anendoscope handle without increasing a length of a resultant lever armsignificantly. Saline and electrical connections (for the heatingchamber 628) enter the handle 610 from the proximal end.

Referring now to FIGS. 6A and 6B, at least one flexible heating chamber628 (comprising a plurality of electrodes) is positioned within thelumen 620 proximate a proximal end of the expandable tip 615. Inaccordance with an embodiment, an outer diameter of the expandable tip615 is less than an inner diameter of a lumen of an ablation needle,such as the needle 4005 of FIGS. 4C and 4D, so that the tip 615 mayslide easily into the lumen of the needle. In some embodiments, thevapor delivery catheter 605 is positioned within the needle, which inturn is positioned within an outer catheter. In some embodiments, theinner diameter of the outer catheter is 3.5 mm, an outer diameter of theneedle 2005 is 3.1 mm and an outer diameter of the vapor deliverycatheter 605 is 2.1 mm.

During operation saline enters the catheter 605 through the proximal endand is converted into steam/vapor that enters the lumen of the needlethrough the expandable tip 615. In embodiments, the catheter 605includes a saline in port 606 for the delivery of saline and a connector607 for an electrical connector for current delivery for the RFcoil/heating chamber 628. The expandable tip 615 gets heated with theflowing vapor and expands radially such that the outer diameter of thetip 615 expands to approximate the inner diameter of the lumen of theneedle. This causes blocking of the space between the expanded tip 615and the needle to form a seal and prevent backflow of vapor between thecatheter 605 and the needle.

In some embodiments, the expandable tip 615 has an expandable metal coilcovered by an insulating thermoplastic such as, but not limited to,PTFE, ePTFE, and silicone. In some embodiments, the metal of theexpandable metal coil is a shape memory metal that exhibits radialexpansion due to a transformation from a martensite state to anaustenite state. In some embodiments, the metal of the expandable metalcoil is steel that exhibits radial expansion due to thermal expansion ofthe steel. FIGS. 6C and 6D illustrate first and second plurality ofexpandable tip designs, in accordance with various embodiments of thepresent specification. FIG. 6C shows first, second, third, fourth andfifth web or mesh patters 630, 631, 632, 633, 634 respectively, for theexpandable tip 615. FIG. 6D shows sixth, seventh, eighth and ninth webor mesh patterns 635, 636, 637, 638 respectively, for the expandable tip615.

Positioning Elements

The positioning elements in FIGS. 7A to 7E have been disclosed in theaforementioned related applications. However, in this case, thepositioning elements have been modified such that, upon the pressurewithin a volume enclosed by two or more positioning elements meeting orexceeding a predefined threshold value, such as 5 atm, the positioningelement deforms by, for example, have one or more components, such as aplate, disc portion, flap, mesh weaving, bend inward or outward from theplanes defining the original deployed shape to increase fluid flow frominside the enclosed volume to an area outside the enclosed volume. Thedeformation may be accomplished by adding a hinge, crease, groove, moreflexible material, or other point of decreased material strength 51between one or more of the components and the rest of the positioningelement.

FIG. 7A illustrates an ablation device with a coaxial catheter design,in accordance with an embodiment of the present specification. Thecoaxial design has a handle 52 a, an infusion port 53 a, an inner sheath54 a and an outer sheath 55 a. The outer sheath 55 a is used toconstrain the positioning device 56 a in the closed position andencompasses ports 57 a. FIG. 7B shows a partially deployed positioningdevice 56 b, with the ports 57 b still within the outer sheath 55 b. Thepositioning device 56 b is partially deployed by pushing the catheter 54b out of sheath 55 b.

FIG. 7C shows a completely deployed positioning device 56 c. Theinfusion ports 57 c are out of the sheath 55 c. The length ‘l’ of thecatheter 54 c that contains the infusion ports 57 c and the diameter ‘d’of the positioning element 56 c are predetermined/known and are used tocalculate the amount of thermal energy needed. FIG. 7D illustrates aconical design of the positioning element. The positioning element 56 dis conical with a known length ‘l’ and diameter ‘d’ that is used tocalculate the amount of thermal energy needed for ablation. FIG. 7Eillustrates a disc shaped design of the positioning element 56 ecomprising circumferential rings 59 e. In some embodiments, positioningelement 56 e has a diameter ranging from 5 mm to 55 mm. Positioningelement 56 e may be of any round shape, and may not necessarily be aperfect circle. The circumferential rings 59 e are provided at a fixedpredetermined distance from the catheter 54 e and are used to estimatethe diameter of a hollow organ or hollow passage in a patient's body.

Hood Vapor Delivery Device

FIG. 8A illustrates a positioning element or attachment 805, inaccordance with an embodiment of the present specification. Thepositioning element 805 is configured as a substantially conicalinsulating hood that is attached proximate to a tip 806 of a catheter807. In some embodiments, the positioning element has length and breadthof 0.5 cm and 5 cm, respectively. In alternative embodiments, thepositioning element 805 is of a different structure, such as includingand not limited to square, rectangular, and parallelogram. The catheter807, in an embodiment, accommodates at least one flexible heatingchamber 808 comprising a plurality of RF electrodes to convert saline,entering a proximal end of the catheter 807, into steam/vapor.

FIG. 8B illustrates a first set of exemplary dimensions for thepositioning element 805, in accordance with an embodiment of the presentspecification. The substantially conical shaped hood or positioningelement 805 has a proximal diameter d₁ of 2.4 mm, a distal diameter d₂of 10 mm and a length ‘l’ of 10 mm. In various embodiments, length Tranges from 0.1 mm to 10 cm and the distal diameter d₂ ranges from 0.1mm to 10 cm. In preferred embodiments, the length ‘l’ and the distaldiameter d₂ range from 5 mm to 5 cm.

FIGS. 8C and 8D illustrate a ball and socket attachment 815 to couplethe positioning element 805 to the tip 806 of the catheter 807, inaccordance with an embodiment of the present specification. The tip 806,at its distal end, has a ball 810 and a front-fire or straight-fire port812. The positioning element 805 has a socket 816 at its proximal end.As shown in FIG. 8D, when the positioning element 805 is attached to thetip 806, the ball 810 is accommodated within the socket 815 to form theball and socket attachment 815.

Referring now to FIGS. 8C and 8D, the ball and socket attachment 815enables ample movement of the positioning element 805 with respect tothe tip 806. In some embodiments, a minimum range of movement, of thepositioning element 805 with respect to the tip 806, is 90 degrees inany direction. The views 820, 822 illustrate the positioning element 805in a closed configuration, such as when the positioning element 805 andthe tip 806 are positioned within an outer catheter. In someembodiments, the positioning element 805 is in a substantiallycylindrical shape of diameter 2.35 mm when in the closed configuration.The views 835, 837 illustrate the positioning element 805 in an open ordeployed configuration, such as when the positioning element 805 and thetip 806 are pushed out of the outer catheter. The positioning element805 acquires a substantially conical shape, in the open or deployedconfiguration, having a base diameter of 12 mm and a side of 7 mm, insome embodiments. In some embodiments, the positioning element 805 is aNiTi tube, web or mesh coated with PTFE, ePTFE or silicone. In someembodiments, the coating, such as of silicone, covers a portion of orthe entirety of the positioning element 805. In some embodiments, thesilicone-coated positioning element 805 has one or more pores withdiameter of each pore ranging from 10 microns to 1000 microns. The poresmay allow for air or steam to vent out from the chamber.

FIG. 8E shows a first perspective view 840, a second perspective view842 and a longitudinal cross-sectional view 845 of the positioningelement 805 attached to the tip 806 of the catheter 807, in accordancewith an embodiment of the present specification. The catheter 807 isshown extending out from an outer catheter 847 such that the positioningelement 805 is in the deployed configuration wherein the positioningelement 805 acquires a substantially conical configuration. The tip 806includes the front-fire or straight-fire port 812 at a distal end and/ortwo pairs of side ports 813 formed diametrically opposed on the sides ofthe tip 806 and positioned proximate the distal end of the tip 806. Insome embodiments, the port 812 has a diameter of 0.9 mm, to allow aguide wire through, while the ports 813 have a diameter of 0.3 mm. Insome embodiments, the catheter 807 has a length of 2500 mm from aproximal end of the catheter 807 to a distal end of the positioningelement 805. In some embodiments, the outer catheter 847 has a length of1800 mm (+/−50 mm) from a proximal end to a distal end of the outercatheter 847.

FIG. 8F illustrates perspective and cross-sectional views of a firstconfiguration 850 of the positioning element 805, in accordance with anembodiment of the present specification. The first configuration 850comprises a substantially cylindrical proximal portion 851 f and asubstantially conical distal portion 852 f In some embodiments, thesubstantially cylindrical proximal portion 851 f is attached, such as byusing glue, to the tip 806 as shown in FIG. 8E. In the firstconfiguration 850, the substantially cylindrical proximal portion 851 fhas a diameter of 2.4 mm and a length of 3 mm, the substantially conicaldistal portion 852 f has a base diameter of 10 mm (+/−1 mm), a length of10 mm (+/−1 mm) and a vertex or opening angle of 41.6 degrees. The totallength of the proximal and distal portions 851 f, 852 f is 13 mm.

FIG. 8G illustrates perspective and cross-sectional views of a secondconfiguration 855 of the positioning element 805, in accordance with anembodiment of the present specification. The second configuration 855comprises a substantially cylindrical proximal portion 851 g and asubstantially conical distal portion 852 g. In some embodiments, thesubstantially cylindrical proximal portion 851 g is attached, such as byusing glue, to the tip 806 as shown in FIG. 8E. In the secondconfiguration 855, the substantially cylindrical proximal portion 851 ghas a diameter of 2.4 mm and a length of 5 mm, the substantially conicaldistal portion 852 g has a base diameter of 15 mm (+/−2 mm), a length of15 mm (+/−5 mm) and a vertex or opening angle of 45.6 degrees. The totallength of the proximal and distal portions 851 g, 852 g is 20 mm.

FIG. 8H illustrates perspective and cross-sectional views of a thirdconfiguration 860 of the positioning element 805, in accordance with anembodiment of the present specification. The third configuration 860comprises a substantially cylindrical proximal portion 851 h and asubstantially conical distal portion 852 h. In some embodiments, thesubstantially cylindrical proximal portion 851 h is attached, such as byusing glue, to the tip 806 as shown in FIG. 8E. In the thirdconfiguration 860, the substantially cylindrical proximal portion 851 hhas a diameter of 2.4 mm, the substantially conical distal portion 852 hhas a base diameter of 20 mm (+/−2 mm), a length of 20 mm (+/−2 mm) anda vertex or opening angle of 47.5 degrees. The total length of theproximal and distal portions 851 h, 852 h is 25 mm.

FIG. 8I illustrates perspective and cross-sectional views of a fourthconfiguration 865 of the positioning element 805, in accordance with anembodiment of the present specification. The fourth configuration 865comprises a substantially cylindrical proximal portion 851 i, asubstantially conical middle portion 852 i and a substantially pyramidaldistal portion 853 i. The substantially pyramidal distal portion 853 iis attached as a base to the substantially conical middle portion 852 i.In an alternate embodiment, the entire positioning element 805 issubstantially pyramidal shape.

In some embodiments, the substantially cylindrical proximal portion 851i is attached, such as by using glue, to the tip 806 as shown in FIG.8E. In the fourth configuration 865, the substantially cylindricalproximal portion 851 i has a diameter of 2.4 mm and a length of 5 mm,the substantially conical middle portion 852 i has a length of 10 mm(+/−2 mm) and a vertex or opening angle of 41.6 degrees, while thesubstantially pyramidal distal portion 853 i has a square base havingeach side of 15 mm (+/−2 mm). The total length of the middle and distalportions 852 i, 853 i is 15 mm (+/−2 mm). The total length of theproximal, middle and distal portions 851 l, 852 i, and 853 i is 20 mm(+/−2 mm). Though FIGS. 8A through 81 depict positioning elements havingconical and pyramidal or rectangular shapes, in other embodiments, thepositioning element or attachments may have other three dimensionalpolygonal or curved shapes.

In various embodiments, the positioning element is mechanicallycompressed for passage into an endoscope channel or an outer catheterand expands when deployed or protruded.

In some embodiments, positioning element 805 comprises a shape memoryalloy, such as Nitinol, thereby allowing it to transform from acompressed configuration for delivery through an endoscope to anexpanded configuration for treatment. In some embodiments, thecompressed configuration approximates a cylindrical shape, to enablepassing through the lumen of an endoscope, attached to the distal end ofthe catheter, and has a 5 mm diameter and a length in a range of 0.5 cmto 5 cm. On expansion, the positioning element 805 has a surface area(from which the steam exits) in a range of 1 cm² to 6.25 cm². In apreferred embodiment, the surface area is square with dimensions of 1.5cm by 1.5 cm. On expansion, the length shortens somewhat so the expandedconfiguration would have a shorter length than the compressedconfiguration. In an embodiment, use of an ablation catheter withpositioning element 805 creates a seal forming an ablation area having aradius of 1 cm, a length of 1 cm, a surface area of 6.28 cm² and atreatment volume of 3.14 cm³.

Referring to the various embodiments of the positioning elementsdescribed in context of FIGS. 7A to 7E, and 8A to 81 , in someembodiments, a range of vapor delivery times is between 1 second to 20seconds for applications of the gastrointestinal (GI) areas. Theduration where the mucosal temperature is >60° C. but <110° C. isbetween 1 second and 10 seconds. Multiple sessions could be repeatedafter an off time of >1 second and <30 minutes. The duration of eachsession could be the same or different. In one embodiment, the durationof two or more sessions is the same, and in another embodiment theduration of a first session is less than a duration of a second session.In another embodiment, a duration of a first session is greater than aduration of a second session.

In various embodiments, multiple sessions with variable times/doses areapplied. In some embodiments, each session is defined by a therapeutictime (T1) and dose (D1). In an embodiment, a first session is deliveredfor a time <T1 at dose T1. Then, the physician waits for a time from 1second to 30 minutes for a certain degree of edema to set in and thendelivers a second with a dose in a range of 1×T1 to 5×T1. Negativepressure, in the form of suction or vacuum, is applied to the ablatedzone after the steam is turned off to increase blood flow to cool thetissue. This increase blood flow could also increase the edemaformation.

FIG. 8J illustrates an ablation catheter 870 with at least one conicalshaped attachment or positioning element 872 and an electrode heatingchamber 874, in accordance with some embodiments of the presentspecification. In various embodiments, the attachment or positioningelement 872 is similar to those described with reference to FIGS. 8Athrough 8I. The attachment or positioning element 872 is positioned atthe distal end of the catheter 870, and at least one port 876 ispositioned at the distal end of the catheter such that the port willdeliver vapor or steam into a volume enclosed by the attachment orpositioning element once the catheter 870 is deployed. In embodiments,distal tip 871 of the catheter 870 comprises the at least one port 876and the at least one positioning element 872 attached to the distal tip871 such that, upon being in an operational configuration, the at leastone positioning element 872 encircles the at least one port 876 and isconfigured to direct all vapor exiting from the at least one port 876.In some embodiments, the attachment or positioning element 872 iscomprised of a shape memory metal and is transformable from a first,compressed configuration for delivery through a lumen of an endoscopeand a second, expanded configuration for treatment. Electrode heatingchamber 874 is positioned within a lumen of the catheter body 878 and,in embodiments, is in a range of 1 mm to 50 cm from the delivery port876. In some embodiments, the catheter 870 includes a filter 880 withmicro-pores which provides back pressure to the delivered steam, therebypressurizing the steam. The predetermined size of micro-pores in thefilter determine the backpressure and hence the temperature of the steambeing generated.

FIG. 9A is a flow chart illustrating a method of ablating a tissueinside a gastrointestinal tract of a patient, in accordance with otherembodiments of the present specification. In embodiments, the method ofFIG. 9A illustrates focal ablation that is performed after observing thepatient following circumferential focused ablation, to treat anyremaining pre-cancerous or cancerous tissue in the esophagus, duodenum,bile duct, and pancreas. In embodiments, ablation catheters disclosed inthe present specification, such as ablation catheter 870 of FIG. 8J, areused to perform the ablation method of FIG. 9A. At 902, an ablationcatheter configured for the gastrointestinal (GI) tract is inserted intothe GI tract of the patient. At 904, a seal is created between anexterior surface of the ablation catheter and an interior wall of the GItract, forming a treatment volume. The seal is created by the expansionof an attachment or positioning element of the ablation catheter, asexplained in the embodiments of the present specification. In someembodiments, the seal is temperature dependent and it breaks when thetemperature within the sealed portion or treatment volume exceeds aspecific temperature. In one embodiment, the specific temperature is 90°C. In some embodiments, the seal is pressure dependent and it breakswhen the pressure within the sealed portion or treatment volume exceedsa specific pressure. In one embodiment, the specific pressure is 5 atm.At 906, vapor is delivered through the ablation catheter into the sealedportion within the GI tract, while the seal is still in place. At 908,the vapor condenses on the tissue under treatment, thereby ablating thetissue.

FIG. 9B is a flow chart illustrating a method of ablating a tissueinside a gastrointestinal tract of a patient, in accordance with otherembodiments of the present specification. In embodiments, the method ofFIG. 9B illustrates focal ablation that is performed after observing thepatient following circumferential focused ablation, to treat anyremaining pre-cancerous or cancerous tissue in the esophagus, duodenum,bile duct, and pancreas. In embodiments, ablation catheters disclosed inthe present specification, such as ablation catheter 870 of FIG. 8J, areused to perform the ablation method of FIG. 9B. At 912, an ablationcatheter configured for the gastrointestinal (GI) tract is inserted intothe GI tract of the patient. At 914, saline with a variable flow rate isintroduced through the ablation catheter into the GI tract. At 916, thesaline is heated using RF energy to generate vapor through the ablationcatheter into the GI tract. In embodiments, the rate of flow of thesaline during vapor delivery is different from flow of the saline duringthe phase where no therapy is delivered. In some embodiments, the rateof flow of saline during the therapy is lower than that during notherapy. In some embodiments, the rate of flow of saline during thetherapy is lower than that during no therapy. At 918, the vaporcondenses on the tissue under treatment, thereby ablating the tissue.

FIG. 9C is a flow chart illustrating a method of using a first ablationcatheter to perform circumferential ablation and then a second ablationcatheter to perform focal ablation, in accordance with some embodimentsof the present specification. It should be noted that, optionally, inother embodiments, a first phase of circumferential ablation using afirst ablation catheter is followed by a second phase of circumferentialablation using the same first ablation catheter, either immediately orat a later date, rather than using the second ablation catheter forfocal ablation. The method of FIG. 9C includes a two-step, or phase,process to ensure complete or near complete ablation of a target tissue.In some embodiments, in a first phase, a patient is treated with a firstablation catheter having two positioning elements to performcircumferential ablation. In embodiments, the first ablation catheterhaving two positioning elements used for the first phase is similar toablation catheter 1991 of FIG. 1K. At step 922, the first ablationcatheter is inserted into a patient's GI tract. A distal positioningelement is expanded at step 924. A proximal positioning element is thenexpanded at step 926, creating a first seal between the peripheries ofthe distal and proximal positioning elements and the GI tract andforming a first enclosed treatment volume between the two positioningelements and the surface of the patient's GI tract. Vapor is deliveredvia ports, positioned on the first ablation catheter between thepositioning elements, into the first enclosed treatment volume at step928. In some embodiments, the system comprises a foot pedal in datacommunication with a controller controlling the catheter, a switch onthe catheter, or a switch on the controller, for controlling vapor flowand step 928 is achieved using the foot pedal in data communication withthe controller, a switch on the catheter, or a switch on the controller.The vapor condenses on the tissue within the first enclosed treatmentvolume at step 930 to circumferentially ablate the tissue. The firstablation catheter having two positioning elements is then removed fromthe GI tract at step 932.

After ablation is performed using the first ablation catheter with twopositioning elements, the ablation area is examined by the physician atstep 934. Upon observing the patient, the physician may identify patchesof tissue requiring focused ablation. A second phase is then performed,wherein a second ablation catheter with a needle or cap, hood, or discattachment or positioning element on the distal end is used for focalablation. The second phase may be performed immediately after the firstphase or at a later date. In embodiments, the second ablation catheterwith a needle or cap, hood, or disc attachment or positioning element onthe distal end used for the second phase is similar to ablation catheter870 of FIG. 8J. (Alternatively, in other embodiments, the physician maywait a period of time, ranging from six weeks to two years, measure theefficacy of the first phase, and then perform a second phase using thesame first ablation catheter for another round of circumferentialablation.) At step 936, the second ablation catheter with a distalattachment or positioning element is inserted into the patient's GItract through the lumen of an endoscope. The distal attachment orpositioning element is expanded at step 938 to create a second sealbetween the periphery of the distal attachment or positioning elementand the GI tract and form a second enclosed treatment volume between thedistal attachment or positioning element and the surface of thepatient's GI tract. Vapor is delivered via at least one port, positionedat the distal end of the catheter, into the second enclosed treatmentvolume at step 940. In some embodiments, the system comprises a footpedal in data communication with a controller controlling the catheter,a switch on the catheter, or a switch on the controller, for controllingvapor flow and step 940 is achieved using the foot pedal in datacommunication with the controller, a switch on the catheter, or a switchon the controller. The vapor condenses on the tissue within the secondenclosed treatment volume at step 942 to focally ablate the tissue. Thesecond ablation catheter having a distal attachment or positioningelement is then removed from the GI tract at step 944.

FIG. 9D is a flow chart illustrating a multi-phase method of using avapor ablation system for duodenal ablation in order to treat obesity,excess weight, eating disorders, metabolic syndrome, diabetes,dyslipidemia, non-alcoholic steatohepatitis (NASH), non-alcoholic fattyliver disease (NAFLD), or a polycystic ovary disease, in accordance withembodiments of the present specification. At step 952, a patient isfirst screened to determine if the patient is a candidate for duodenalablation using the ablation systems of the present specification. Fordiabetes, metabolic syndrome, obesity or excess weight, in variousembodiments, the patient must have a BMI (Body Mass Index) of 25 orgreater (overweight being 25-30, obese being 30 and above, and morbidobesity being above 35). In accordance with various aspects of thepresent specification, a patient with diabetes must have HbA1c levels ofat least 6.5 gm %, fasting blood glucose levels of at least 126 mg/dL ora random plasma glucose level of at least 200 mg/dL, 2-hour plasmaglucose levels of at least 200 mg/dL (11.1 mmol/L) during an oralglucose tolerance test (OGTT), or a fasting insulin concentration of atleast 5.7 μU/mL (109 pmol/L). For insulin resistance, in variousembodiments, a patient must have a homeostatic model assessment ofinsulin resistance (HOMA-IR) of at least 1.6. In accordance with variousaspects of the present specification, a patient with dyslipidemia musthave a serum triglyceride concentration of at least 130 mg/dL (1.47mmol/L) or a ratio of triglyceride to high-density lipoprotein (HDL)cholesterol concentration of greater than 3.0 (1.8 SI units).

Patients screened at step 952 and determined to be candidates forduodenal ablation then proceed with an ablation procedure using a vaporablation system in accordance with embodiments of the presentspecification. The vapor ablation system is configured to delivercircumferential ablation of a patient's duodenum or small intestine totreat any one or more of the conditions listed above. The vapor ablationsystem comprises a controller having at least one processor in datacommunication with at least one pump and a catheter connection port influid communication with the at least one pump. At step 954 of a firstphase of treatment, a proximal end of a first catheter is connected tothe catheter connection port to place the first catheter in fluidcommunication with the at least one pump. The first catheter comprisesat least two positioning elements separated along a length of thecatheter and at least two ports positioned between the at least twopositioning elements, wherein each of the at least two positioningelements has a first configuration and a second configuration, andwherein, in the first configuration, each of the at least twopositioning elements is compressed within the catheter and in the secondconfiguration, each of the at least two positioning elements is expandedto be at least partially outside the catheter. At step 956, the firstcatheter is positioned inside a patient such that, upon being expandedinto the second configuration, a distal one of the at least twopositioning elements is positioned within in the patient's smallintestine and a proximal one of the at least two positioning elements isproximally positioned more than 1 cm from the distal one of the at leasttwo positioning elements. Then, at step 958 each of the at least twopositioning elements is expanded into their second configurations. Atstep 960, the controller is activated, wherein, upon activation, thecontroller is configured to cause the at least one pump to deliversaline into at least one lumen in the first catheter and, wherein, uponactivation, the controller is configured to cause an electrical currentto be delivered to at least one electrode positioned within the at leastone lumen of the first catheter. The electrical current causes theelectrode to heat and contact of the saline with the heating electrodeconverts the saline to vapor, or steam, which is delivered via the atleast two ports to circumferentially ablate target tissue.

In various embodiments, the vapor is delivered to treat at least 1-15 cmof contiguous or non-contiguous small intestine mucosa. In variousembodiments, the vapor is delivered to treat at least 50% of acircumference of small intestine. In various embodiments, the vapor doseis characterized at least one of: having an energy of 5-25 J/cm²,delivered over 1-60 seconds, delivered at an energy rate of 5-2500cal/sec, delivered such that the total dose is 5-40 calories/gram oftissue to be ablated, delivered to elevate a target tissue temperatureabove 60° C. but less than 110° C., has a vapor temperature between 99°C. and 110° C., or delivered such that a pressure in a small intestineis less than 5 atm, and preferably less than 1 atm.

At step 962, the controller shuts off the delivery of saline andelectrical current after a time period ranging from 1 to 60 seconds. Inembodiments, the controller automatically shuts off the delivery ofsaline and electrical current. The controller is repeatedly activated atstep 964 to deliver saline into the lumen and electrical current to theat least one electrode until the physician terminates the procedure. Insome embodiments, the system further comprises a foot pedal in datacommunication with the controller, a switch on the catheter, or a switchon the controller, for controlling vapor flow and step 964 is achievedusing the foot pedal in data communication with the controller, a switchon the catheter, or a switch on the controller. The first catheter isremoved from the patient at step 966 to complete a first phase oftreatment.

At step 968, the physician then waits for at least six weeks after thecompletion of the first phase to allow the ablation therapy to takeeffect before evaluating the efficacy of the treatment. After at leastsix weeks, at step 970, a post-first phase evaluation is performedwherein the efficacy of the first phase of treatment is determined bymeasuring physiological parameters relating to the conditions beingtreated and comparing the measured values to desired therapeutic goalsor endpoints.

In various embodiments, ablation therapy is provided to achieve thefollowing therapeutic goals or endpoints for patients with obesity,excess weight, eating disorders, dyslipidemia, or diabetes and a firstphase of treatment is considered successful for these patients if anyone or more of the following therapeutic goals or endpoints is reached:a total body weight of the patient decreases by at least 1% relative toa total body weight of the patient before ablation; an excess bodyweight of the patient decreases by at least 1% relative to an excessbody weight of the patient before ablation; a total body weight of thepatient decreases by at least 1% relative to a total body weight of thepatient before ablation and a well-being level of the patient does notdecrease more than 5% relative to a well-being level of the patientbefore ablation; an excess body weight of the patient decreases by atleast 1% relative to an excess body weight of the patient beforeablation and a well-being level of the patient does not decrease morethan 5% relative to a well-being level of the patient before ablation; apre-prandial ghrelin level of the patient decreases by at least 1%relative to a pre-prandial ghrelin level of the patient before ablation;a post-prandial ghrelin level of the patient decreases by at least 1%relative to a post-prandial ghrelin level of the patient beforeablation; an exercise output of the patient increases by at least 1%relative to an exercise output of the patient before ablation; aglucagon-like peptide-1 level of the patient increases by at least 1%relative to a glucagon-like peptide-1 level of the patient beforeablation; a leptin level of the patient increases by at least 1%relative to a leptin level of the patient before ablation; the patient'sappetite decreases, over a predefined period of time, relative to thepatient's appetite before ablation; a peptide YY level of the patientincreases by at least 1% relative to a peptide YY level of the patientbefore ablation; a lipopolysaccharide level of the patient decreases byat least 1% relative to a lipopolysaccharide level of the patient beforeablation; a motilin-related peptide level of the patient decreases by atleast 1% relative to a motilin-related peptide level of the patientbefore ablation; a cholecystokinin level of the patient increases by atleast 1% relative to a cholecystokinin level of the patient beforeablation; a resting metabolic rate of the patient increases by at least1% relative to a resting metabolic rate of the patient before ablation;a plasma-beta endorphin level of the patient increases by at least 1%relative to a plasma-beta endorphin level of the patient beforeablation; an HbA1c level of the patient decreases by at least 0.3%relative to an HbA1c level of the patient before ablation; atriglyceride level of the patient decreases by at least 1% relative to atriglyceride level of the patient before ablation; a total bloodcholesterol level of the patient decreases by at least 1% relative to atotal blood cholesterol level of the patient before ablation; a glycemialevel of the patient decreases by at least 1% relative to a glycemialevel of the patient before ablation; a composition of the person's gutmicrobiota modulates from a first state before ablation to a secondstate after ablation, wherein the first state has a first level ofbacteroidetes and a first level of firmicutes, wherein the second statehas a second level of bacteroidetes and a second level of firmicutes,wherein the second level of bacteroidetes is greater than the firstlevel of bacteroidetes by at least 3%, and wherein the second level offirmicutes is less than the first level of firmicutes by at least 3%;or, a cumulative daily dose of the patient's antidiabetic medicationsdecreases by at least 10% relative to a cumulative daily dose of thepatient's antidiabetic medications before ablation.

In various embodiments, ablation therapy is provided to achieve thefollowing therapeutic goals or endpoints for patients with dyslipidemiaand a first phase of treatment is considered successful for thesepatients if any one or more of the following therapeutic goals orendpoints is reached: a lipid profile of the patient improves by atleast 10% relative a lipid profile of the patient before ablation,wherein lipid profile is defined at least by a ratio of LDL cholesterolto HDL cholesterol, and improve is defined as a decrease in the ratio ofLDL cholesterol to HDL cholesterol; an LDL-cholesterol level of thepatient decreases by at least 10% relative to an LDL-cholesterol levelof the patient before ablation; or, a VLDL-cholesterol level of thepatient decreases by at least 10% relative to a VLDL-cholesterol levelof the patient before ablation.

In various embodiments, ablation therapy is provided to achieve thefollowing therapeutic goals or endpoints for patients with non-alcoholicsteatohepatitis (NASH) or non-alcoholic fatty liver disease (NAFLD), anda first phase of treatment is considered successful for these patientsif any one or more of the following therapeutic goals or endpoints isreached: at least a 10% decrease in either ALT or AST levels relative toALT or AST levels before ablation; at least a 10% improvement in serumferritin level or an absolute serum ferritin level of less than 1.5 ULN(upper limit normal) relative to serum ferritin levels before ablation;at least a 5% improvement in hepatic steatosis (HS) or less than 5% HSrelative to HS levels before ablation, as measured on liver biopsy; atleast a 5% improvement in HS or less than 5% HS relative to HS levelsbefore ablation, as measured by magnetic resonance (MR) imaging, eitherby spectroscopy or proton density fat fraction; at least a 5%improvement in an NAFLD Fibrosis Score (NFS) relative to an NFS beforeablation; at least a 5% improvement in an NAFLD Activity Score (NAS)relative to an NAS before ablation; at least a 5% improvement in aSteatosis Activity Fibrosis (SAF) score relative to an SAF score beforeablation; at least a 5% decrease in a mean annual fibrosis progressionrate relative to a mean annual fibrosis progression rate beforeablation, as measured by histology, Fibrosis-4 (FIB-4) index, aspartateaminotransferase (AST) to platelet ratio index (APRI), serum biomarkers(Enhanced Liver Fibrosis (ELF) panel, Fibrometer, FibroTest, orHepascore), or imaging (transient elastography (TE), MR elastography(MRE), acoustic radiation force impulse imaging, or supersonic shearwave elastography); at least a 5% decrease in circulating levels ofcytokeratin-18 fragments relative to circulating levels ofcytokeratin-18 fragments before ablation; at least a 5% improvement inFIB-4 index, aspartate aminotransferase (AST]) to platelet ratio index(APRI), serum biomarkers (Enhanced Liver Fibrosis (ELF) panel,Fibrometer, FibroTest, or Hepascore), or imaging (transient elastography(TE), MR elastography (MRE), acoustic radiation force impulse imaging,or supersonic shear wave elastography) relative to FIB-4 index,aspartate aminotransferase (AST]) to platelet ratio index (APRI), serumbiomarkers (Enhanced Liver Fibrosis (ELF) panel, Fibrometer, FibroTest,or Hepascore), or imaging (transient elastography (TE), MR elastography(MRE), acoustic radiation force impulse imaging, or supersonic shearwave elastography) before ablation; at least a 5% decrease in liverstiffness relative to liver stiffness before ablation, as measured byvibration controlled transient elastography (VCTE/FibroScan); animprovement in NAS by at least 2 points, with at least 1-pointimprovement in hepatocellular ballooning and at least 1-pointimprovement in either lobular inflammation or steatosis score, and noincrease in the fibrosis score, relative to NAS, hepatocellularballooning, lobular inflammation, steatosis, and fibrosis scores beforeablation; at least a 5% improvement in NFS scores relative to NFS scoresbefore ablation; or, at least a 5% improvement in any of the abovelisted NAFLD parameters as compared to a sham intervention or a placebo.

If any one of the above therapeutic goals or endpoints is met, therapyis completed at step 972 and no further ablation is performed. If noneof the above therapeutic goals or endpoints are met, then the entireablation procedure and evaluation, less the screening process, andcomprising steps 954-970, is repeated for a second therapy phase, andsubsequent therapy phases if therapeutic goals or endpoints are stillnot met, waiting at least six weeks each time between each ablationprocedure and each evaluation.

FIG. 9E is a flow chart illustrating a multi-stage method of using avapor ablation system for treating cancerous or precancerous esophagealtissue, in accordance with various embodiments of the presentspecification. The vapor ablation system comprises a controller havingat least one processor in data communication with at least one pump anda catheter connection port in fluid communication with the at least onepump. At step 953, a proximal end of a first catheter is connected tothe catheter connection port to place the first catheter in fluidcommunication with the at least one pump, wherein the first cathetercomprises at least two positioning elements separated along a length ofthe catheter and at least two ports positioned between the at least twopositioning elements, wherein each of the at least two positioningelements has a first configuration and a second configuration, andwherein, in the first configuration, each of the at least twopositioning elements is compressed within the catheter and in the secondconfiguration and each of the at least two positioning elements isexpanded to be at least partially outside the catheter. At step 955, thefirst catheter is positioned inside a patient such that, upon beingexpanded into the second configuration, a distal one of the at least twopositioning elements is positioned adjacent the patient's esophagus anda proximal one of the at least two positioning elements is proximallypositioned more than 1 cm from the distal one of the at least twopositioning elements. At step 957, each of the at least two positioningelements is expanded into their second configurations. At step 959, thecontroller is activated, wherein, upon activation, the controller isconfigured to cause the at least one pump to deliver saline into atleast one lumen in the first catheter and, wherein, upon activation, thecontroller is configured to cause an electrical current to be deliveredto at least one electrode positioned within the at least one lumen ofthe first catheter. The electrical current causes the electrode to heatand contact of the saline with the heating electrode converts the salineto vapor, or steam, which is delivered via the at least two ports tocircumferentially ablate target tissue. In some embodiments, during thefirst stage of treatment, the at least two positioning elements,together with the esophageal tissue, define a first enclosed volumewherein at least one of the at least two positioning elements ispositioned relative the esophageal tissue to permit a flow of air out ofthe second enclosed volume when the vapor is delivered.

In various embodiments, the vapor is delivered to treat at least 1-15 cmof contiguous or non-contiguous small intestine mucosa. In variousembodiments, the vapor is delivered to treat at least 50% of acircumference of small intestine. In various embodiments, the vapor doseis characterized at least one of: having an energy of 5-25 J/cm²,delivered over 1-60 seconds, delivered at an energy rate of 5-2500cal/sec, delivered such that the total dose is 5-40 calories/gram oftissue to be ablated, delivered to elevate a target tissue temperatureabove 60° C. but less than 110° C., has a vapor temperature between 99°C. and 110° C., or delivered such that a pressure in a small intestineis less than 5 atm, and preferably less than 1 atm.

In various embodiments, the vapor is delivered to treat at least 1-15 cmof contiguous or non-contiguous small intestine mucosa. In variousembodiments, the vapor is delivered to treat at least 50% of acircumference of small intestine. In various embodiments, the vapor doseis characterized at least one of: having an energy of 5-25 J/cm²,delivered over 1-60 seconds, delivered at an energy rate of 5-2500cal/sec, delivered such that the total dose is 5-40 calories/gram oftissue to be ablated, delivered to elevate a target tissue temperatureabove 60° C. but less than 110° C., has a vapor temperature between 99°C. and 110° C., or delivered such that a pressure in a small intestineis less than 5 atm, and preferably less than 1 atm.

At step 961, the controller shuts off the delivery of saline andelectrical current. In embodiments, the controller automatically shutsoff the delivery of saline and electrical current. Optionally, at step963, the controller is reactivated to deliver saline into the lumen ofthe first catheter and electrical current to the electrode until thephysician terminates the procedure. The catheter is removed from thepatient at step 965 to complete a first stage of treatment.

The physician waits for at least six weeks at step 967 before evaluatingthe efficacy of the first stage. After at least six weeks, at step 969,a post-first stage evaluation is performed wherein the efficacy of thefirst stage of treatment is determined by measuring physiologicalparameters relating to the conditions being treated and comparing themeasured values to desired therapeutic goals or endpoints.(Alternatively, in other embodiments, a visible evaluation is performedimmediately after completion of the first stage and, if deemed necessarybased on the visual observation, a second stage of treatment using asecond catheter is performed before waiting at least six weeks.)

If the desired therapeutic goals or endpoints have not been achieved, asecond stage of therapy is performed. At step 971, a proximal end of asecond catheter is connected to the catheter connection port to placethe second catheter in fluid communication with the at least one pump,wherein the second catheter comprises a distal tip having at least oneport and at least one positioning element attached to the distal tipsuch that, upon being in an operational configuration, the at least onepositioning element encircles the at least one port and is configured todirect all vapor exiting from the at least one port. At step 973, thesecond catheter is positioned inside the patient such that a distalsurface of the at least one positioning element is positioned adjacentthe patient's esophagus. Optionally, the at least one positioningelement is expandable from a first, collapsed configuration to anexpanded, operational configuration and, at step 975, the at least onepositioning element is expanded into the operation configuration. Atstep 977, the controller is activated, wherein, upon activation, thecontroller is configured to cause the at least one pump to deliversaline into at least one lumen in the second catheter and, wherein, uponactivation, the controller is configured to cause an electrical currentto be delivered to at least one electrode positioned within the at leastone lumen of the second catheter. The electrical current causes theelectrode to heat and contact of the saline with the heating electrodeconverts the saline to vapor, or steam, which is delivered via the atleast one port to focally ablate target tissue. In some embodiments,during the second stage of treatment, the at least one positioningelement, together with the esophageal tissue, defines a second enclosedvolume wherein the at least one positioning element is positionedrelative the esophageal tissue to permit a flow of air out of the secondenclosed volume when the vapor is delivered.

In various embodiments, the vapor is delivered to treat at least 1-15 cmof contiguous or non-contiguous small intestine mucosa. In variousembodiments, the vapor is delivered to treat at least 50% of acircumference of small intestine. In various embodiments, the vapor doseis characterized at least one of: having an energy of 5-25 J/cm²,delivered over 1-60 seconds, delivered at an energy rate of 5-2500cal/sec, delivered such that the total dose is 5-40 calories/gram oftissue to be ablated, delivered to elevate a target tissue temperatureabove 60° C. but less than 110° C., has a vapor temperature between 99°C. and 110° C., or delivered such that a pressure in a small intestineis less than 5 atm, and preferably less than 1 atm.

At step 979, the controller shuts off the delivery of saline andelectrical current after a time period ranging from 1 to 60 seconds. Inembodiments, the controller automatically shuts off the delivery ofsaline and electrical current. Optionally, in some embodiments, thecontroller is repeatedly activated at step 981 to deliver saline intothe lumen and electrical current to the at least one electrode until thephysician terminates the procedure. In some embodiments, the systemfurther comprises a foot pedal in data communication with thecontroller, a switch on the catheter, or a switch on the controller, forcontrolling vapor flow and step 981 is achieved using the foot pedal indata communication with the controller, a switch on the catheter, or aswitch on the controller. The second catheter is removed from thepatient at step 983 to complete the second stage of treatment. In someembodiments, evaluations are performed at least six weeks to two yearsafter completion of the second stage to determine efficacy of the secondstage and, if desired therapeutic goals or endpoints are not achieved,further first and/or second stages, with further evaluations, may beperformed as needed.

Therapeutic Pressure Profiles for Ablation Therapy

In various embodiments, the catheters of the present specificationmeasure and monitor pressure of the steam/vapor throughout an ablationtherapy and maintain the pressure below a predefined limit, such as 5atm or 5 psi, in order to limit the amount of thermal energy transferredto the tissues during the therapy.

In accordance with an aspect of the present specification, the energyconsumed by the heating chamber is reflective of vapor pressuregenerated. FIG. 10A shows first and second graphs illustrating energyconsumption profile by a heating chamber (flexible heating chamber withRF electrodes or inductive coil based heating chamber) and pressureprofile of vapor generated during an ablation therapy, in accordancewith an embodiment of the present specification. The first graph 1005illustrates the power or energy consumption profile (in Watts) of theheating chamber with respect to time while the second graph 1007illustrates the vapor pressure profile at an inlet of the heatingchamber with respect to time. As shown in FIG. 10B the ablation therapyis stopped when the vapor pressure reaches above the predefined limit,such as 5 psi, and an alert 1008 is generated.

In accordance with another aspect of the present specification, thetemperature of vapor correlates with the vapor pressure measured alongthe pathway of the vapor. FIG. 10C shows third and fourth graphsillustrating a temperature profile of vapor and a pressure profile ofvapor generated during an ablation therapy, in accordance with anembodiment of the present specification. The third graph 1010illustrates the temperature profile of vapor with respect to time whilethe fourth graph 1012 illustrates the vapor pressure profile along thevapor pathway with respect to time.

FIGS. 10D through 10P illustrate a plurality of exemplary vapor pressurebased therapy profiles during ablation, in accordance with embodimentsof the present specification. The pressure therapy profiles in each ofthe figures are shown as graphs having time (in seconds) on an X-axisand pressure (in atmospheres, atm) on a Y-axis.

FIG. 10D illustrates a pressure therapy profile 1015 wherein vapordelivery is initiated and pressure is raised to a desired maximumpressure 1017, such as 3 atm. The vapor pressure is maintained at themaximum pressure 1017 for a predefined time, such as 10 seconds, andthereafter the vapor delivery is stopped allowing the pressure to returnto baseline 1018.

FIG. 10E illustrates the pressure therapy profile 1015 being repeatedfor a plurality of cycles, wherein the desired maximum pressure 1017 issame for each cycle. FIG. 10F illustrates the pressure therapy profile1015 being repeated for a plurality of cycles wherein the desiredmaximum pressure 1017 is customized for each cycle. For example, thedesired maximum pressure 1017 is: 2 atm for the first cycle 1020 a, 2.5atm for the second cycle 1020 b and 3 atm for the third cycle 1020 c.Thereafter, the desired maximum pressure 1017 is: maintained at 3 atmfor the fourth cycle 1020 d, 2.5 atm for the fifth cycle 1020 e and 2atm for the sixth cycle 1020 f. In other words, the desired maximumpressure 1017 is increased and decreased for individual cycles 1020 athrough 1020 f by increasing and decreasing the flow of vapor to createcustom treatment profile.

FIGS. 10G, 10H and 10I illustrate pressure therapy profiles 1025, 1026and 1027, wherein the pressure of vapor delivery is gradually increasedto reach a target pressure 1028 at which time, the vapor delivery isaborted allowing the pressure to return to a baseline pressure 1029.FIG. 10J illustrates a plurality of cycles of at least one of thepressure therapy profiles 1025, 1026 and 1027, wherein for each cyclethe therapy pressure builds up to the desired target pressure 1028 andthen stops to return to the baseline pressure 1029 and recycles.

FIG. 10K illustrates a pressure therapy profile 1030, wherein thepressure of vapor delivery is rapidly increased to reach a targetpressure 1032 during a predefined period of time after which, the vapordelivery is gradually decreased allowing the pressure to slowly returnto a baseline pressure 1034.

FIG. 10L illustrates a plurality of cycles of a pair of first and secondpressure profiles 1035, 1037 wherein the first pressure profile 1035 hasa first maximum pressure 1036 and the second pressure profile 1037 has asecond maximum pressure 1038. In some embodiments, the first maximumpressure 1036 is higher than the second maximum pressure 1038. Thus, ahigher pressure of vapor delivery is cycled with a lower pressure ofvapor delivery.

FIG. 10M illustrates a plurality of cycles of a pressure profile 1040wherein for each cycle the vapor is delivered to a pressure P₁ for apredetermined duration of time. Next, the vapor delivery is aborted andthe pressure is allowed to decrease to a pressure P₂, below baseline1042 for another predetermined duration of time. Thereafter, the vapordelivery is reinitiated and delivered to a pressure P₃ for yet anotherpredetermined duration of time. Finally, the vapor delivery is abortedallowing the pressure to return to baseline pressure 1042. In someembodiments, the pressure P₁ is comparable to or approximately equal toa sum of P₂ and P₃.

FIG. 10N illustrates a plurality of cycles of a pressure profile 1045wherein for each cycle the vapor is delivered to a pressure P₁ for apredetermined duration of time. Next, the vapor delivery is aborted andthe pressure is allowed to decrease to a pressure P₃, below baseline1047 for another predetermined duration of time. Now, the vapor deliveryis reinitiated and delivered to a pressure P₂ for another predeterminedduration of time. Next, the vapor delivery is aborted and the pressureis allowed to decrease to the pressure P₃, below baseline 1047 foranother predetermined duration of time. Thereafter, the vapor deliveryis reinitiated and delivered to the pressure P₂ for anotherpredetermined duration of time. Finally, the vapor delivery is abortedallowing the pressure to return to the baseline pressure 1047. In someembodiments, the pressure P₁ is comparable to or approximately equal toa sum of P₂ and P₃.

FIG. 10O illustrates a plurality of cycles of a pressure profile 1050wherein for each cycle the vapor is delivered to a pressure P₁ for apredetermined duration of time. Next, the vapor delivery is aborted andthe pressure is allowed to decrease to a pressure P₃, below baseline1052 for another predetermined duration of time. Now, the vapor deliveryis reinitiated and delivered to a pressure P₂ for another predeterminedduration of time. Next, the vapor delivery is aborted and the pressureis allowed to decrease to the pressure P₃, below baseline 1052 foranother predetermined duration of time. Thereafter, the vapor deliveryis reinitiated and delivered to the pressure P₁ for anotherpredetermined duration of time. Finally, the vapor delivery is abortedallowing the pressure to return to the baseline pressure 1052. In someembodiments, the pressure P₁ is comparable to or approximately equal toa sum of P₂ and P₃.

FIG. 10P illustrates a plurality of cycles of a pressure profile 1055wherein for each cycle the vapor is delivered to a pressure P₁ for apredetermined duration of time. Next, the vapor delivery is aborted andthe pressure is allowed to decrease to a pressure P₂, below baseline1057 for another predetermined duration of time. Now, the vapor deliveryis reinitiated and delivered to the pressure P₁ for anotherpredetermined duration of time. Next, the vapor delivery is aborted andthe pressure is allowed to decrease to the pressure P₂, below baseline1057 for another predetermined duration of time. Thereafter, the vapordelivery is reinitiated and delivered to the pressure P₁ for anotherpredetermined duration of time. Finally, the vapor delivery is abortedallowing the pressure to return to the baseline pressure 1057. In someembodiments, the pressure P₁ is substantially greater than the pressureP₂.

FIGS. 11A and 11B illustrate single and coaxial double balloon catheters1145 a, 1145 b in accordance with embodiments of the presentspecification. The catheters 1145 a, 1145 b include an elongate body1146 with a proximal end 11511 and a distal end 1153 and a first lumen1155, a second lumen 1156, and a third lumen 1157 within. In anembodiment, the elongate body 1146 is insulated. The catheters 1145 a,1145 b include at least one positioning element 1148 proximate theirdistal end 1153. In various embodiments, the positioning element is aninflatable balloon. In some embodiments, the catheters include more thanone positioning element. As shown in FIG. 11B, the coaxial catheter 1145b includes an outer catheter 1146 b that accommodates the elongate body1146.

In the embodiments depicted in FIGS. 11A, 11B, the catheters 1145 a,1145 b include a proximal first inflatable balloon 1147 and a distalsecond inflatable balloon 1148 positioned proximate the distal end ofthe body 1146 with a plurality of infusion ports 1149 located on thebody 1146 between the two balloons 1147, 1148. It should be appreciatedthat, while balloons are preferred, other positioning elements, aspreviously described, may be used.

The body 1146 includes a first lumen 1155 (extending along a portion ofthe entire length of the body 1146) in fluid communication with a firstinput port 1165 at the proximal end 11511 of the catheter body 1146 andwith said proximal first balloon 1147 to inflate or deflate the proximalfirst balloons 1147, 1148 by supplying or suctioning air through thefirst lumen 1155. In an embodiment, use of a two-balloon catheter asshown in FIGS. 11A and 11B results in the creation of a seal andformation of a treatment area having a radius of 3 cm, a length of 9 cm,a surface area of 169.56 cm2 and a treatment volume of 254.34 cm3. Thebody 1146 includes a second lumen 1156 (extending along the entirelength of the body 1146) in fluid communication with a second input port1166 at the proximal end 1152 of the catheter body 1146 and with saiddistal second balloon 1148 to inflate or deflate the distal secondballoon 1148 by supplying or suctioning air through the second lumen1156. In another embodiment, the body includes only a first lumen for influid communication with the proximal end of the catheters and the firstand second balloons for inflating and deflating said balloons. The body1146 also includes an in-line heating element 1150 placed within asecond third lumen 1157 (extending along the length of the body 1146) influid communication with a third input port 1167 at the proximal end1152 of the catheter body 1146 and with said infusion ports 1149. In oneembodiment, the heating element 1150 is positioned within the thirdlumen 1157, proximate and just proximal to the infusion ports 1149. Inan embodiment, the heating element 1150 comprises a plurality ofelectrodes. In one embodiment, the electrodes of the heating element1150 are folded back and forth to increase a surface contact area of theelectrodes with a liquid supplied to the third lumen 1157. The secondthird lumen 1157 serves to supply a liquid, such as water/saline, to theheating element 1150.

In various embodiments, a distance of the heating element 1150 from anearest port 1149 ranges from 1 mm to 50 cm depending upon a type oftherapy procedure to be performed.

A fluid pump, an air pump and an RF generator are coupled to theproximate end of the body 1146. The air pump propels air via said firstand second inputs 1165, 1166 through the first and second lumens toinflate the balloons 1147, 1148 so that the catheters 1145 a, 1145 b areheld in position for an ablation treatment. The fluid pump pumps aliquid, such as water/saline, via said third input 1167 through thesecond third lumen 1157 to the heating element 1150. The RF generatorsupplies power an electrical current to the electrodes of the heatingelement 1150, thereby causing the electrodes to heat and converting theliquid (flowing through around the heating element 1150) into vapor. Thegenerated vapor exits the ports 1149 for ablative treatment of targettissue. In embodiments, the supply of liquid and electrical current, andtherefore delivery of vapor, is controlled by a microprocessor.

FIG. 11C is a flow chart of a plurality of steps of using the catheters1145 a, 1145 b to perform ablation in a body lumen, such as in Barrett'sesophagus of a patient, in accordance with an embodiment of the presentspecification. At step 1171, insert the catheters 1145 a, 1145 b into abody lumen. In one embodiment, the body lumen is an esophagus of apatient. At step 1172, inflate the balloons 1147, 1148 to demarcate atarget ablation area, such as Barrett's esophagus, and position thecatheters 1145 a, 1145 b such that the infusion ports 1149 arepositioned in the target ablation area, such as in a portion ofBarrett's esophagus. At step 1173, provide liquid, such as water orsaline, to a proximal end of the catheters 1145 a, 1145 b. Finally, atstep 1174, provide electrical current to the electrodes of the heatingelement 1150 to heat the electrodes and convert the liquid to vaporwherein the generated vapor is delivered through the infusion ports 1149to ablate the target tissue, such as Barrett's esophagus of the patient.In various embodiments, steps 1173 and 1174 are performed simultaneouslyor step 1174 is performed prior to step 1173.

FIG. 12A is an assembled schematic view of a vapor generation system1200 comprising an induction heating unit 1205 coupled or attachedfluidically in-series (or in-line) with, and at a proximal end of, acatheter handle 1210, in accordance with an embodiment of the presentspecification, while FIGS. 12B and 12C are exploded views of componentsupstream and downstream to the induction heating unit 1205. Referring toFIGS. 12A, 12B and 12C simultaneously, the induction heating unit 1205includes an induction coil 1212 surrounding a heating chamber 1215 that,in turn, houses a metallic or ferromagnetic core 1220 within. Inembodiments, the induction coil 1212 comprises Litz electromagneticconducing wire wound in a tight helical fashion. A power cable 1207extends from the induction coil 1212 to a power generator. The inductioncoil 1212 is positioned in a thermally insulated external “soft skin”housing 1202. In embodiments, the housing 1202 is a thermally stable,over molded component consisting of low to medium durometerthermoplastic elastomer material such as Kraton®. Optionally, theinduction heating unit 1205 further comprises at least one thermocouple1214 to measure input and output temperature at the heating chamber1215.

In embodiments, the heating chamber 1215 is manufactured from hightemperature resistant materials such as, but not limited to, PEEK(polyetheretherketone) or polysulfone. The core 1220 may be fabricatedfrom conductive metals or alloys such as, but not limited to, carbonsteel, stainless steel or other ferro-magnetic materials such asMu-metal (soft magnetic alloy with high Nickel/Iron content for highpermeability and efficient electromagnetic conductance). Composition ofan exemplary Mu metal may approximately be 77% nickel, 16% iron, 5%copper and 2% chromium or molybdenum.

The induction heating unit 1205 is reusable and securely locks onto theheating chamber 1215. In some embodiments, the induction heating unit1205 snap fits over the heating chamber 1215. In some embodiments, theheating chamber 1215 incorporates male détentes on its outer surfacewhich lock onto female détentes on an internal surface of the housing1202. In this way, the induction heating unit 1205 positively locks overthe heating chamber 1215, insulating the operator from the heat affectedzone during ablation. In accordance with aspects of the presentspecification, once loaded over the heating chamber 1215, the inductionheating unit 1205 can be rotated, about its longitudinal axis, based onoperator preference, to ensure that the workspace around a catheter,associated with the catheter handle 1210, is clutter-free.

The core 1220 located inside the heating chamber 1215 serves as aheating element to convert saline/water, received through a saline/waterin-feed tube 1225 at a proximal end of the induction heating unit 1205,to steam once electricity is passed through the induction coil 1212. Thesaline/water in-feed tube 1225 tracks from a disposable pump head andincorporates a first thumb latch 1237 operated first female couplerhousing body 1236 at its distal end. The first female coupler housingbody 1236 is configured to lock onto a first male coupler end cap 1230extending from a proximal portion of the heating chamber 1215.

In embodiments, the core 1220 is solid or tubular. Optionally, the core1220 may have fenestrations or a helical screw thread on its outerdiameter to assist with water to steam conversion. The core 1220 islocked/held inside the heating chamber 1215 via the first male couplerend cap 1230. The first male coupler end cap 1230 connects the heatingchamber 1215 to the first female coupler housing body 1236. Once thefirst male coupler 1230 has been inserted into the first female couplerhousing body 1236, a water tight seal is created which preventswater/vapor leakage from the assembly. To de-couple the first male andfemale coupler parts, the first thumb latch 1237 is depressed and theparts are axially separated. The first male coupler end cap 1230 iswater/steam contacting and is fabricated from a high temp resistantmaterial such as PEEK or polysulfone, for example.

As shown in FIGS. 12A and 12C, a 3-way flow control valve 1240, such asa solenoid valve in an embodiment, is located downstream of theinduction heating unit 1205 between the heating chamber 1215 and asecond male coupler 1245 that connects the induction heating unit 1205to the catheter handle 1210. FIGS. 13A and 13B respectively illustratede-energized and energized states of a 3-way flow control solenoid valve1340 (similar to the valve 740). The valve 1340 enables the followingtypes of flow operations: a) normally closed flow operation—as shown inFIG. 13A, when the valve 1340 is de-energized, a pressure port 1305 isclosed and an exhaust port 1310 is connected to a cylinder port 1315.When the valve 1340 is energized, the exhaust port 1310 is closed andthe pressure port 1305 is connected to the cylinder port 1315; b)normally open flow operation—as shown in FIG. 13B, when the valve 1340is de-energized, the pressure port 1305 is connected to the cylinderport 1315 and the exhaust port 1310 is closed. When the valve 1340 isenergized, the pressure port 1305 is closed and the cylinder port 1315is connected to the exhaust port 1310.

Referring back to FIGS. 12A through 12C, at the start of an ablationprocedure, as the ablation system 1200 is being set up and “primed”’there will be a residual reservoir of water already in the system 1200.This water (or condensate) must be drained from the system 1200 and anamount of high temperature vapor injected to a target ablation site,maximized. To prime the system 1200, the power generator is switched onand a duty cycle activated. Condensate flow is diverted to a condensatedrainage line or tube 1250 until such time as only vapor exits thisline. Once this occurs, a generator controller will energize thesolenoid valve 1240 to an open position (FIG. 13B). In this way, thesystem 1200 is primed with vapor and drained of condensate, such thatonly vapor is delivered from the heating chamber 1215 to the catheter.

As shown in FIG. 12C, the second male coupler 1245 connects the valve1240 to a second thumb latch 1255 operated second female coupler housingbody 1260 positioned at a proximal end of the catheter handle 1210. Inaccordance with aspects of the present specification, the entireinduction heating unit 1205 assembly is rotatable around a longitudinalaxis of the catheter to ensure that associated power cables and tubinglines can be positioned as desired by the operator.

FIG. 14A shows a dual-balloon, dual shaft, multi-lumen catheter system1400 while FIG. 14B shows two elongate catheter shafts 1405, 1407 forthe catheter system 1400, in accordance with embodiments of the presentspecification. Referring to FIGS. 14A and 14B simultaneously, thecatheter system 1400 comprises distal and proximal inflatable anchoringballoons 1410, 1412 that, in one embodiment, are respectively coupledwith two different catheter shafts 1405, 1407. The catheter shafts 1405,1407 are of a multi-lumen construction and are manufactured from polymermaterial which is capable of maintaining performance under continuousexposure to vapor/steam and temperatures ranging from 110° C. to 120°C., such as PEEK or polysulfone.

The outer shaft 1407 is connected to the proximal balloon 1412 while theinner shaft 1405 is connected to the distal balloon 1410. The outershaft 1407 has a first lumen 1408 to accommodate the inner shaft 1405and a second lumen 1409 to allow inflation fluid (such as air) to flowinto the proximal balloon 1412 for inflation or be suctioned fordeflation. The inner shaft 1405 telescopes axially within the firstlumen 1408. The inner shaft 1405 has a first (vapor) lumen 1415 toenable ablation fluid, such as vapor, to flow through the cathetersystem 1400 and be released from a plurality of exit ports 1440 locatedbetween the distal and proximal balloons 1410, 1412 and a second lumen1417 to allow inflation fluid (such as air) to flow into the distalballoon 1410 for inflation or be suctioned for deflation. Accordingly,both catheter shafts 1405, 1407 are capable of axial movementindependently of each other. In this way, a distance between the distaland proximal balloons 1410, 1412 may be adjusted before or during anablation procedure, thereby adjusting a length of a coagulation/ablationzone 1420. In some embodiments, the length of the zone 1420 ranges from4 cm to 6 cm. In some embodiments, the lumens 1409 and 1417 have a“smiley” shaped cross-section. However, in alternate embodiments, thecross-section can be of other shapes such as, but not limited to,circular, square or rectangular.

Once positioned at an appropriate ablation treatment location, thedistal and proximal balloons 1410, 1412 are inflated and anchored—suchas, for example, against a wall of an esophagus—both distally andproximally. This ensures that a defined, controlled coagulation zone1420 is achieved prior to the creation and delivery of vapor to thetreatment site. In some embodiments, the diameters of both proximal anddistal balloons 1410, 1412 are capable of being inflated to cover arange of desired esophageal diameters (ranging between 18 mm to 32 mm)to be treated. Once the balloons have been inflated in position, vaporis generated via the induction heating unit 1205 (FIG. 12A) at aproximal end of the catheter handle 1210 (FIG. 12A) outside a patientand injected through the vapor lumen 1415 of the inner shaft 1405.

A portion of the catheter shaft system 1400 between the balloons 1410,1412 contains a number of eyeholes, configured around the circumferenceof the shafts 1405, 1407. These eyeholes serve as vapor exit ports 1440.FIGS. 14C and 14D respectively illustrate first and second eyeholepatterns 1430, 1435, in accordance with embodiments of the presentspecification. The first eyeholes pattern 1430 has a plurality of exitports 1440 formed on both sides of the inner shaft 1405 into the first(vapor) lumen 1415, positioned approximately 90 degrees about a circularaxis on either side of the distal balloon inflation lumen 1417, whilethe second eyeholes pattern 1435 has a plurality of exit ports 1440 on asingle side, opposite the distal balloon inflation lumen 1417, of theinner shaft 1405 into the first (vapor) lumen 1415. Vapor is deliveredfrom these ports 1440, contacting and treating diseased tissueencapsulated in the coagulation/ablation zone 1420 demarcated by bothballoons 1410, 1412.

FIG. 14E illustrates a transverse cross-sectional view of a multi-lumenshaft 1450 e of the catheter system 1400 of FIG. 14A, in accordance withan embodiment of the present specification. The shaft 1450 e comprises afirst inner most lumen 1452 e that allows water/saline to flow thereinand also accommodates a heating element, such as the flexible heatingchamber (comprising a plurality of electrodes) or an induction heatingchamber (comprising an induction coil), a second lumen 1454 e provides apathway for inflation of the distal balloon 1410 or control of a distalpositioning element, a third lumen 1456 e that is configured as an innersheath and a fourth lumen 1458 e provides a pathway for inflation of theproximal balloon 1412 or control of a proximal positioning element. Inembodiments the heating element is positioned substantially close to theplurality of vapor exit ports 1440. In various embodiments, the heatingelement is positioned not more than 6 inches back from a distal end ofthe proximal balloon 1412.

FIGS. 15A and 15B illustrate a telescoping catheter handle 1500 for usewith the dual-balloon, dual shaft, multi-lumen catheter system 1400 ofFIG. 14A, in accordance with embodiments of the present specification.Referring now to FIGS. 14A, 14B, 15A and 15B simultaneously, the handle1500 comprises a first handle component 1505 in a first positionrelative to a second handle component 1510, in accordance with oneembodiment of the present specification. In one embodiment, the firsthandle component 1505 has an elongate body with a proximal end anddistal end and comprises a thumb latch 1503 operated female coupler 1502at the proximal end. In one embodiment, the second handle component 1510has an elongate body with a proximal end and a distal end. The secondhandle component 1510 telescopes in and out of the distal end of thefirst handle component 1505 thereby adjusting the distance between thedistal and proximal balloons 1410, 1412. A connector 1515 is included atthe distal end of the second handle component 1510 and includes a luercomponent 1517 (at a distal end of the connector 1515) for attaching thecatheter handle 1500 to a working channel port of an endoscope handle.The shaft of the dual-balloon, multi-lumen catheter system 1400 extendsbeyond the distal end of the second handle component 1510.

A first inlet port 1525 is located at the first handle component 1505and attached to the inner shaft 1405 to inflate/deflate the distalballoon 1410. A second inlet port 1530 is located at the second handlecomponent 1510 and attached to the outer shaft 1407 to inflate/deflatethe proximal balloon 1412. The first handle component 1505 includes afirst thumbscrew 1532 to extend the catheter system 1400 beyond theendoscope and the second handle component 1510 includes a secondthumbscrew 1535 to adjust a length of the coagulation/ablation zone1420.

In the first position depicted in FIG. 15A, the first handle component1505 is positioned most proximally relative to the second handlecomponent 1510. Referring to FIG. 15B, the second handle component 1510includes a plurality of markings 1533 along its body. In one embodiment,the markings 1533 are numbers. The first handle component 1505 includesa window 1540 proximate its distal end which aligns with one of saidmarkings as the first handle component 1505 is moved longitudinallyrelative to the second handle component 1510. The marking 1533 in thewindow 1540 indicates the length of the catheter system 1400 extendedbeyond a distal end of the working channel of the endoscope and into abody lumen of a patient. FIG. 15B illustrates the catheter handle 1500with the first handle component 1505 in a second position relative tothe second handle component 1510. The marking 1533 in window 1540indicates to an operator that the first handle component 1505 is in itsmost distal position relative to the second handle component 1510 andthat the catheter system 900 is fully extended within the body lumen ofthe patient.

Referring now to FIG. 15C along with FIGS. 12A, 12B, 12C, the catheterhandle 1500 at its distal end is attached to a working channel port ofthe endoscope 1545 by means of the luer component 1517 or a latch-typelocking mechanism in various embodiments. At its proximal end thecatheter handle 1500 is connected to the induction heating unit 1205through the thumb latch 1503 operated female coupler 1502. FIG. 15Cshows a disassembled view of the inducting heating unit 1205illustrating an assembly of the heating chamber 1215 and the core 1220over which the housing 1202, comprising the induction coil 1212, isslidably attached. The power cable 1207 extends from the induction coil1212 to a power generator. The 3-way flow control valve 1240 is alsoshown positioned between the catheter handle 1500 and the inductionheating unit 1205. The thumb latch 1503 operated female coupler 1502provides the operator with a mechanism to attach/detach the valve 1240and the assembly of the heating chamber 1215 and the core 1220 from thecatheter handle 1500.

FIG. 15D is a disassembled view of the second handle component 1510,FIG. 15E is a perspective view of the second handle component 1510separated out from the first handle component 1505, while FIG. 15F is across-sectional view of the second handle component 1510. Referring nowto FIGS. 15D, 15E, 15F along with FIGS. 14A and 14B, the second handlecomponent 1510 houses a tube 1550 that, at its proximal end, isconnected to the second inlet port 1530. The catheter system 1400 passesalong the second handle component 1510 as shown in FIG. 15E, 15F. Thesecond inlet port 1530 is in fluid communication via a skive 1419 intothe second lumen 1409 of the outer shaft 1407 to enableinflation/deflation of the proximal balloon 1412.

FIG. 15G is a break-away view of the first handle component 1505 whileFIG. 15H is a cross-sectional view of the first handle component 1505.Referring now to FIGS. 15G, 15H along with FIGS. 14A, 14B, the firstinlet port 1525 is attached (threaded, in an embodiment) into a manifold1555 and is in fluid connection with the second lumen 1417 of the innershaft 1405 to enable inflation/deflation of the distal balloon 1410. Thehousing 1560 of the female coupler 1502 attaches to a male luer 1559 ofthe manifold 1555.

FIG. 16A shows a single multi-lumen shaft 1600 for the dual-balloon,multi-lumen catheter system 1400 of FIG. 14A, in accordance withembodiments of the present specification. Referring now to FIGS. 16A and14A simultaneously, the distal and proximal balloons 1410, 1412 arecoupled with the single multi-lumen shaft 1600. As a result, a distancebetween the balloons 1410, 1412 is fixed and thus, a length of thecoagulation/ablation zone 1420 is also fixed. A distal portion of theshaft 1600 between the balloons 1410, 1412 contains a number of eyeholesthat serve as vapor exit ports 1440.

In accordance with an embodiment, the shaft 1600 includes five lumensand is manufactured from polymer material which is capable ofmaintaining performance under continuous exposure to vapor/steam andtemperatures ranging from 110° C. to 120° C., such as PEEK orpolysulfone. A first lumen 1605 allows ablation fluid, such assteam/vapor, to flow therethrough and exit from the vapor exit ports1440. A second lumen 1610 is in fluid communication with the distalballoon 1410 to enable an inflation fluid, such as air, to flow or besuctioned therethrough for inflation/deflation of the balloon 1410. Athird lumen 1615 is in fluid communication with the proximal balloon1412 to enable the inflation fluid, such as air, to flow or be suctionedtherethrough for inflation/deflation of the balloon 1412. Fourth andfifth lumens 1620, 1625 serve as auxiliary lumens for the first (steam)lumen 1605. The fourth and fifth lumens 1620, 1625 are in fluidcommunication with the first lumen 1605 at a distal portion of the shaft1600 to allow flow of vapor from the first lumen 1605 through fourth andfifth lumens 1620, 1625 and out exit ports 1440 to ablate target tissue.

FIG. 16B illustrates a pattern of vapor exit ports 1440 at the distalportion of the shaft 1600 in accordance with an embodiment of thepresent specification. As shown, the vapor exit ports 1440 are arrangedon first and second sides 1630, 1635 along a longitudinal axis of theshaft 1600 such that the two sides 1630, 1635 are 180° opposed. As shownin FIGS. 16C, 16D, the steam or vapor lumen 1605 is located in thecenter of the shaft 1600. To inject vapor from the central steam lumen1605, the ports 1440 are drilled/laser cut through the outer wall 1640of the shaft 1600, through the auxiliary lumens 1620, 1625 and throughthe inner wall 1645 of the steam lumen 1605.

FIGS. 16E and 16F illustrate, respectively, perspective and break-awayviews of a non-telescopic catheter handle 1650 for use with the singlemulti-lumen shaft 1600, in accordance with embodiments of the presentspecification. Referring to FIGS. 16E and 16F along with FIG. 14A, thecatheter handle 1650 has an elongate body 1652 comprising: a first inletport 1655 attached to a first manifold 1656 that holds the port 1655 influid communication with the second lumen 1610 to enableinflation/deflation of the distal balloon 1410; and a second inlet port1660 attached to a second manifold 1662 that holds the port 1660 influid communication with the third lumen 1615 to enableinflation/deflation of the proximal balloon 1412. In some embodiments,the first and second manifolds 1656, 1662 are configured to be coupledto the shaft 1600 and fabricated from PEEK/polysulfone. First and secondtubing lines (not shown) are respectively connected to the first andsecond ports 1655, 1660. Proximal ends of both tubing lines areconnected to two independent inflation pumps which are housed in agenerator. Inflation and deflation (if desired) of both balloons 1410,1412 is controlled via both lines. In embodiments, both tubing lines areflexible polymer extrusions and are disposable.

A connector 1666 is positioned at a distal end of the body 1652 and aluer component is attached at a distal end of the connector 1666 toenable the handle 1650 to be attached to a working channel port of anendoscope. The catheter shaft 1600 extends beyond the distal end of theconnector.

A thumbscrew 1665 is positioned proximate a distal end of the handle1650 to enable adjustment of the shaft 1600 beyond the endoscope whenthe handle 1600 is attached to a working channel of the endoscope. Athumb latch 1670 operated female coupler 1675 is positioned at aproximal end of the handle 1650 to enable an induction heating unit(such as the unit 1205) to be attached in-series or in-line to thehandle 1650 (similar to as illustrated in FIG. 15C). The second manifold1662 is fluidically connected to the housing body of the female coupler1675.

In accordance with aspects of the present specification, it is preferredthat the thumbscrew 1665 and the thumb latch 1670 be facing in the samedirection so that orientation is towards the operator when the handle1650 is locked onto the endoscope. It is also preferred that both ports1655, 1660 are positioned or oriented approximately 90 degrees opposedto the thumb latch 1670 so that they provide favorable ergonomics forthe operator and do not interfere with handle 1650 manipulation duringan ablation procedure.

In accordance with an aspect of the present specification, FIG. 17Cshows an induction heating unit being removably mounted onto anendoscope, while FIGS. 17A and 17B illustrate perspective views of aclamp in accordance with embodiments of the present specification.Referring now to FIGS. 17A, 17B and 17C along with FIG. 12A, theinduction heating unit 1205, comprising an assembly of the heatingchamber 1215 (with the core 1220) and the induction coil 1212, ismounted on a body of an endoscope 1705, below a biopsy port bifurcation1707 on the endoscope 1705. Mounting the induction heating unit 1205 tothis location reduces the moment arm and weight on a catheter handle1710 and moves a number of components away from the immediate handleworking space around the thumbscrews 1715, 1720 as well as distal andproximal balloon inflation ports 1725, 1730 for inflation/deflation ofdistal and proximal balloons of a dual-balloon multi-lumen catheter(such as catheter system 1400 of FIG. 14A). In some embodiments, thecatheter handle 1710 is a telescopic handle (such as the handle 1500 ofFIG. 15A) while in other embodiments the catheter handle 1710 is anon-telescopic handle (such as the handle 1650 of FIG. 16E).

The induction heating unit 1205 is removably attached to a main shaft ofthe endoscope 1705 using a soft grip clamp 1735. In an embodiment, theclamp 1735 consists of a soft, deformable, rubber grip 1740 attached toa rigid polymeric frame 1745 which incorporates a bracket 1750 to mountthe induction heating unit 1205. In an embodiment, the bracket 1750 isconfigured as a C-clamp. As shown in FIG. 17D, the heating chamber 1215,the core 1220 and the two male coupler end caps 1230 are pre-assembledas a module 1770, in accordance with an embodiment. Next, the module1770 is slidably inserted into the housing 1202, comprising theinduction coil 1212, thereby forming the induction heating unit 1205.Subsequently, the induction heating unit 1205 is slid into anapproximately C-shaped space 1775 of the bracket 1750.

Referring back to FIGS. 17A, 17B and 17C, once the induction heatingunit 1205 is slidably mounted into the C-clamp the assembly is loaded onto the shaft of the endoscope 1705, below the biopsy port. Thedeformable nature of the rubber grip 1740 provides a secure attachmentto the endoscope 1705. This orientation of the clamp 1735 can be easilyadjusted to suit preferred orientation of the induction heating unit1205 during an ablation procedure. The clamp 1735 may be removed bysimply pulling outward on the bracket assembly.

A disposable water/saline tube line 1755 connects to a thumb latchoperated female coupler 1756 at a proximal end of the induction heatingunit 1205 while a disposable vapor delivery tube line 1760 is connectedto the unit 1205 via a thumb latch operate female coupler 1757 at adistal end of the unit 1205 and to the handle 1710 via another thumblatch operated female coupler 1762 at a proximal end of the handle 1710.In various embodiments, the vapor delivery tube line 1760 is made ofPEEK, polysulfone, high temperature Nylon, polycarbonate or polyimidematerial. In some embodiments, this tube may also be braided reinforcedto make the tubing more resistant to kinking during the procedure. Itshould be appreciated that, although not shown in FIG. 17C, a 3-way flowcontrol valve, such as valve 1240, is positioned between the unit 1205and the handle 1710.

FIG. 18 is an illustration of an embodiment of a disposable tubing set1800 to be used with the ablation systems of the present specification.In an embodiment, the tubing set 1800 includes a rigid plastic spike1801 to puncture a saline bag or reservoir 1802, flexible polymerictubing 1803, a pressure sensor 1804, and a coupler with thumb latch1805. The pressure sensor 1804 connects to a microcontroller on thevapor generator and is used to monitor and control pressure in thesystem once vapor generation and delivery has been initiated. Thecoupler with thumb latch 1805 is configured to securely lock the tubing1803 to the proximal end of the induction heating unit. Alternatively,in an embodiment, the coupler with thumb latch 1805 is replaced with amale coupler to connect with the female coupler 1756 at the proximal endof the inducting heating unit 1205 depicted in FIG. 17C. In anembodiment, the tubing set 1800 also includes a flow control componentwith thumb dial 1806 for controlling a rate flow from the saline bag orreservoir 1802.

The tubing set 1800 also includes first and second disposable inflationline tubes that are flexible polymer extrusions. Distal ends of thefirst and second inflation line tubes respectively connect to distal andproximal balloon inflation ports of a catheter handle. Proximal ends ofthe first and second inflation line tubes are connected to twoindependent inflation pumps. Inflation and deflation (if desired) ofboth distal and proximal balloons is controlled via the first and secondinflation line tubes.

FIG. 19 is an illustration of a telescoping catheter handle 1910attached to an endoscope 1950, in accordance with an embodiment of thepresent specification. A proximal balloon inflation line 1905 isconnected to a proximal balloon inflation port 1906 for inflation of aproximal balloon and a distal balloon inflation line 1908 is attached toa distal balloon inflation port 1909 for inflation of a distal balloon.An induction heating unit 1915 is attached to the proximal end of thecatheter handle 1910 and includes a power line 1917 for providingelectrical current to the wire of the induction coil. A saline deliveryline 1920 is connected to the proximal end of the induction heating unit1915. A three-way valve 1912 is included between the catheter 1910 andinduction heating unit 1915 for priming the system to remove residualwater before vapor generation.

FIG. 20A is an assembled view of a vapor generator 2050, FIG. 20B is apartial disassembled view of the vapor generator 2050, FIG. 20C is adisassembled view of a disposable pump of the vapor generator 2050, FIG.20D is an assembled view of the disposable pump and FIG. 20E shows thedisposable pump fluidically connected to other components of the vaporgenerator 2050, in accordance with an embodiment of the presentspecification. Referring to FIGS. 20A through 20E, simultaneously, thevapor generator 2050 comprises a water/saline bag or reservoir 2055fluidically attached to a first tube 2060. At one end, the first tube2060 has a rigid plastic spike 2056 to puncture the reservoir 2055 whileat another end the first tube 2050 has a first latch operated femaleconnector 2058 for quick connection to a first male coupler end cap 2065of an in-feed tube portion 2070 of a disposable pump 2075.

The disposable pump 2025 comprises a pump head 2072 that attaches to apump motor housing 2074. The first tube 2060 feeds water/saline from thereservoir 2055 to the pump 2075. Pressurized water/saline, output by thepump 2075, is carried forward by a second tube 2080 that attaches to asecond male coupler end cap 2085, of a tube portion 2090 of the pump2075, by means of a second female coupler 2095. The second tube 2080supplies pressurized water/saline to a heating chamber of an inductionheating unit.

Gastrointestinal Ablation

FIG. 21 illustrates an ablation catheter placed in an uppergastrointestinal tract with Barrett's esophagus to selectively ablatethe Barrett's tissue, in accordance with an embodiment of the presentspecification. Referring to FIG. 21 , the upper gastrointestinal tractcomprises Barrett's esophagus 2141, gastric cardia 2142,gastroesophageal junction 2143 and displaced squamo-columnar junction2144. The area between the gastroesophageal junction 2143 and thedisplaced squamo-columnar junction 2144 is Barrett's esophagus 2141,which is targeted for ablation. Distal to the cardia 2142 is the stomach2145 and proximal to the cardia 2142 is the esophagus 2146. The ablationdevice is passed into the esophagus 2146 and the balloons 2110, 2112 arepositioned such that the balloon 2112 is placed in the gastric cardia2142 abutting the gastroesophageal junction 2143. This affixes theablation catheter and its infusion ports (shown in FIG. 4A) in thecenter of the esophagus 2146 and allows for uniform delivery of theablative agent to the Barrett's esophagus 2141. It should be appreciatedthat the fluid delivery port 2127 and the suction port 2132 arepositioned at a site away from the tissue being ablated so that a) thedelivery of fluid does not significantly interfere with delivery of theablative agent and b) the suction process does not result in suction ofthe ablative agent.

FIG. 22 is a flowchart illustrating a method of ablation of Barrett'sesophagus in accordance with one embodiment of the presentspecification. Referring to FIG. 22 , in the first step 2201, anendoscopy is performed on the patient to measure the length of Barrett'sesophagus in the patient. Thereafter in step 2202, the measured lengthis input into a processor of an ablation system used to calculate theamount of ablative energy needed to ablate the Barrett's esophagus. Inanother embodiment, the measured length is used as a reference to selecta catheter of appropriate ablation segment length to approximate thelength of Barrett's esophagus. Next, in step 2203, a catheter having afirst positioning balloon at its distal end and a second positioningballoon at its proximal end is passed through the endoscope channel oralongside the endoscope channel such that the distal balloon ispositioned proximate a cardia tissue of a patient and the proximalballoon is positioned proximate the top of the Barrett's esophagus.

In the next step 2204, the two balloons are inflated to a set pressure(P1) and the diameter of the Barrett's esophagus is measured using theproximal balloon. This diameter is manually or automatically input intothe processor and a surface area of the Barrett's segment to be ablatedis calculated, as shown in step 2205.

Next, in step 2206, one or more cycles of vapor is delivered to theesophageal mucosa through one or more vapor delivery ports on thecatheter at a temperature in a range of 90 to 100° C. to ablate theBarrett's esophagus. In step 2207, the balloon pressures during thedelivery of ablative agent are maintained at a pressure P2 which isgreater than or equal to pressure P1. Optionally, in step 2208, theballoons are deflated to a pressure P3 which is less than or equal topressure P1 between the cycles of ablation. Finally, the endoscope andthe catheter are removed after the ablation is complete in step 2209.

It should be appreciated that any ablation catheter or system of thepresent specification, used to ablate tissue in an organ, may be usedwith a controller, wherein the controller is configured to limit apressure generated by ablation fluid, such as steam/vapor, within theorgan to less than 5 atm or 100 psi.

FIG. 23A illustrates deflated 2340 d, lateral inflated 23401, andfrontal inflated 2340 f views of an ablation catheter 2340 having aninsulating membrane 2349 for duodenal ablation, in accordance with oneembodiment of the present specification. In some embodiments, thecatheter 2340 comprises a water-cooled catheter having a proximalinflatable balloon 2342 and a distal inflatable balloon 2344 with aninsulating membrane 2349 which extends from a proximal end of theproximal balloon 2342 to a distal end of the distal balloon 2344. Aplurality of vapor delivery ports 2343 are positioned on the catheter2340 between the proximal balloon 2342 and distal balloon 2344. Once theballoons 2342, 2344 are inflated, as depicted in lateral view 23401, thestretching of the insulating membrane 2349 between the balloons 2342,2344 causes the catheter 2340 to bow, helping to position the insulatingmembrane over the ampulla of vater, thereby providing a protectiveshield over the ampulla during vapor ablation therapy.

FIG. 23B illustrates the ablation catheter 2340 of FIG. 23A deployed ina duodenum 2350 of a patient, in accordance with one embodiment of thepresent specification. The catheter 2340 has been deployed through aworking channel of an endoscope 2341 such that the distal inflatableballoon 2344 is positioned in the distal duodenum 2350 d, proximal tothe jejunum 2352, and the proximal inflatable balloon 2342 is positionedin the proximal duodenum 2350 p. The insulating membrane 2349 ispositioned over the ampulla of Vater 2351 to prevent ablative agent 2345delivered to the duodenum 2350 from damaging said ampulla 2351. Proximalportions 2349 p and distal portions 2349 d of the insulating membrane2349 are attached to the proximal inflatable balloon 2342 and distalinflatable balloon 2344 respectively, such that the insulating membrane2349 becomes stretched to conform to the shape of the duodenum 2350 oncethe catheter 2340 is deployed.

In various embodiments, ablation therapy provided by the vapor ablationsystems of the present specification is delivered to treat a variety ofconditions and efficacy of treatment is determined by measuring certainphysiological parameters, as further described below, in a range of timefrom at least six weeks to two years after treatment. If the therapeuticendpoints are not achieved after a period of at least six weeks,ablation therapy is repeated. Physiological parameters are then measuredafter at least another six weeks, and ablation therapy may be repeatedand evaluated in a similar six week cycle, until the desired therapeuticendpoint is achieved.

In various embodiments, ablation therapy, particularly duodenalablation, provided by the vapor ablation systems of the presentspecification is delivered to treat at least one of fatty liver,non-alcoholic fatty liver disease (NAFLD), non-alcoholicsteatohepatitis, type II diabetes, metabolic syndrome, overweightpatients, and obesity. In various embodiments, ablation therapy,particularly duodenal ablation, provided by the vapor ablation systemsof the present specification is delivered to achieve the followingtherapeutic endpoints: treat type II diabetes by achieving at least a10% reduction in HbA1c or fasting blood glucose level when measured atleast six weeks after treatment; treat metabolic syndrome; or treathyperlipidemia by achieving at least a 5% reduction in either totalcholesterol or LDL or triglyceride or at least a 5% improvement in theHDK cholesterol, as measured at least six weeks after treatment.

In case of the treatment for fatty liver or Non-Alcoholic Fatty LiverDisease (NAFLD)/Non-Alcoholic Steatohepatitis, ablation therapy,particularly duodenal ablation, provided by embodiments of the vaporablation systems of the present specification is delivered to achievethe following therapeutic endpoints, as measured at least six weeksafter treatment: at least a 10% decrease in either ALT or AST levels; arelative improvement of 10% in serum Ferritin level or an absolute levelof no more than 1.5 ULN (upper limit normal); at least a 5% relativeimprovement in hepatic steatosis (HS), or no more than 5% HS as measuredon liver biopsy; at least a 5% relative improvement in HS as measured bymagnetic resonance (MR) imaging, either by spectroscopy or protondensity fat fraction; at least a 5% relative improvement in NAFLDFibrosis Score (NFS); at least a 5% relative improvement in NAFLDActivity Score (NAS); at least a 5% relative improvement in SteatosisActivity Fibrosis (SAF) score; at least 10% of patients showing adecrease in the mean annual fibrosis progression rate as measured byhistology, Fibrosis-4 (FIB-4) index, aspartate aminotransferase (AST) toplatelet ratio index (APRI)), serum biomarkers (Enhanced Liver Fibrosis(ELF) panel, Fibrometer, FibroTest, and Hepascore), or imaging(Transient Elastography (TE), MR Elastography (MRE), acoustic radiationforce impulse imaging, and supersonic shear wave elastography); at leasta 5% relative improvement in circulating levels of cytokeratin-18fragments; at least a 5% relative improvement in FIB-4 index, aspartateaminotransferase (AST) to platelet ratio index (APRI), serum biomarkers(Enhanced Liver Fibrosis (ELF) panel, Fibrometer, FibroTest, andHepascore), or imaging (TE, MRE, acoustic radiation force impulseimaging, and supersonic shear wave elastography); at least a 5% relativeimprovement in liver stiffness measured by vibration controlledtransient elastography (VCTE (FibroScan)); at least 10% of patientsshowing an improvement in NAS by 2 points with at least 1-pointimprovement in hepatocellular ballooning and 1-point improvement ineither the lobular inflammation or steatosis score, and no increase inthe fibrosis score; at least 10% of patients showing an improvement inthe NFS scores; and at least 5% of patients showing an improvement inany of the above listed NAFLD parameter as compared to a shamintervention or a placebo. In various embodiments, the relativetherapeutic goals and endpoints are provided relative to one or morepre-treatment levels of the correspondingly stated physiologicalindicators.

In various embodiments, ablation therapy, particularly duodenalablation, provided by the vapor ablation systems of the presentspecification is delivered to treat obesity in a person by achieving oneof the following therapeutic endpoints, as measured at least six weeksafter treatment: a total body weight of the person reduces by at least1% relative to a total body weight of the person before ablation; anexcess body weight of the person reduces by at least 1% relative to anexcess body weight of the person before ablation; a total body weight ofthe person reduces by at least 1% relative to a total body weight of theperson before ablation and a well-being level of the person does notreduce more than 5% relative to a well-being level of the person beforeablation; an excess body weight of the person reduces by at least 1%relative to an excess body weight of the person before ablation and awell-being level of the person does not reduce more than 5% relative toa well-being level of the person before ablation; after at least oneablation, a pre-prandial ghrelin level of the person reduces by at least1% relative to a pre-prandial ghrelin level of the person beforeablation; after at least one ablation, a post-prandial ghrelin level ofthe person reduces by at least 1% relative to a post-prandial ghrelinlevel of the person before ablation; after at least one ablationsession, exercise output of the patient increases by at least 1%relative to the exercise output of the patient before ablation; after atleast one ablation, a glucagon-like peptide-1 level of the personincreases by at least 1% relative to a glucagon-like peptide-1 level ofthe person before ablation; after at least one ablation, a leptin levelof the person increases by at least 1% relative to a leptin level of theperson before ablation; after at least one ablation, the patient'sappetite decreases, over a predefined period of time, relative to thepatient's appetite before ablation; after at least one ablation, apeptide YY level of the person increases by at least 1% relative to apeptide YY level of the person before ablation; after at least oneablation, a lipopolysaccharide level of the person reduces by at least1% relative to a lipopolysaccharide level of the person before ablation;after at least one ablation, a motilin-related peptide level of theperson reduces by at least 1% relative to a motilin-related peptidelevel of the person before ablation; after at least one ablation, acholecystokinin level of the person increases by at least 1% relative toa cholecystokinin level of the person before ablation; after at leastone ablation, a resting metabolic rate of the person increases by atleast 1% relative to a resting metabolic rate of the person beforeablation; after at least one ablation, a plasma-beta endorphin level ofthe person increases by at least 1% relative to a plasma-beta endorphinlevel of the person before ablation; after at least one ablation, theperson's level of hemoglobin A1c decreases by an amount equal to atleast 0.3%; after at least one ablation, a triglyceride level of theperson decreases by at least 1% relative to a triglyceride level of theperson before ablation; after at least one ablation, a total bloodcholesterol level of the person decreases by at least 1% relative to atotal blood cholesterol level of the person before ablation; after atleast one ablation, a glycemia level of the person decreases by at least1% relative to a glycemia level of the person before ablation; after atleast one ablation, a composition of the person's gut microbiotamodulates from a first state to a second state, wherein the first statehas a first level of bacteroidetes and a first level of firmicutes,wherein the second state has a second level of bacteroidetes and asecond level of firmicutes, wherein the second level of bacteroidetes isgreater than the first level of bacteroidetes by at least 3%, andwherein the second level of firmicutes is less than the first level offirmicutes by at least 3%; after at least one ablation, the cumulativedaily dose of a patient's antidiabetic medications decrease by at least10%; after at least one ablation, a patient's lipid profile improves byat least 10%; after at least one ablation, a patient's LDL-cholesteroldecreases by at least 10%; and, after at least one ablation, a patient'sVLDL-cholesterol decreases by at least 10%. In various embodiments, therelative therapeutic goals and endpoints are provided relative to one ormore pre-treatment levels of the correspondingly stated physiologicalindicators.

The ablation systems and methods of the present specification,particularly duodenal ablation, may be used to treat a conditionincluding any one of obesity, excess weight, eating disorders, metabolicsyndrome and diabetes, NASH/NAFLD or a polycystic ovary disease. Inaccordance with various aspects of the present specification, theablation systems and methods, particularly duodenal ablation, enabletreating people with a BMI (Body Mass Index) of 25 or greater(overweight being 25-30, obese being 30 and above, and morbid obesitybeing above 35). In accordance with various aspects of the presentspecification, the ablation systems and methods, particularly duodenalablation, also enable treating people with HbA1c levels of at least 6.5gm %, fasting blood glucose levels of at least 126 mg/dL or a randomplasma glucose level of at least 200 mg/dL, a 2-hour plasma glucoselevel of at least 200 mg/dL (11.1 mmol/L) during an oral glucosetolerance test (OGTT). The ablation systems and methods, particularlyduodenal ablation, can also be used to treat nondiabetic, normotensiveoverweight individuals, with a serum triglyceride concentration of atleast 130 mg/dL (1.47 mmol/L), a ratio of triglyceride to high-densitylipoprotein (HDL) cholesterol concentration of at least 3.0 (1.8 SIunits), and fasting insulin concentration of at least 5.7 μU/mL (109pmol/L). The ablation systems and methods, particularly duodenalablation, can also be used to treat patients with insulin resistancedefined as homeostatic model assessment of insulin resistance (HOMA-IR)of at least 1.6, or associated disorders. The ablation systems andmethods, particularly duodenal ablation, can also be used to treatpatients with dyslipidemia.

FIG. 24 is a flowchart illustrating a method of ablation of a colon inaccordance with one embodiment of the present specification. Referringto FIG. 24 , the first step 2401 includes inserting an endoscope intothe lower gastrointestinal tract of a patient. Next, in step 2402, acatheter of an ablation device is passed through the endoscope, whereinthe catheter includes a hollow shaft through which an ablative agent cantravel, at least one positioning element, at least one input port forreceiving an ablative agent, and at least one infusion port fordelivering the ablative agent. The catheter is passed through theendoscope such that the positioning element is positioned proximate tothe colonic tissue to be ablated. In an embodiment, the ablation deviceincludes a controller comprising a microprocessor for controlling thedelivery of the ablative agent. The positioning element is deployed inthe colonic lumen of the patient such that the positioning elementcontacts a portion of the colon of the patient and the catheter andinfusion port are positioned within the colonic lumen in step 2403. Inone embodiment, the positioning element is positioned over andencompasses the colonic tissue. Finally, in step 2406, an ablative agentis delivered through the infusion port to ablate the colonic tissue.

Optionally, a sensor is used to measure at least one dimension of thecolon in step 2404 and the measurement is used to determine the amountof ablative agent to be delivered in step 2405.

In various embodiments, ablation therapy provided by the vapor ablationsystems of the present specification is delivered to achieve thefollowing therapeutic endpoints for duodenal ablation: maintain a tissuetemperature at 100° C. or less; ablate at least 50% of a surface area ofa duodenal mucosa; ablate a duodenal mucosa without significant ablationof an ampullary mucosa; reduce fasting blood glucose by at least 5%relative to pre-treatment fasting blood glucose; reduce HbA1c by atleast 5% relative to pre-treatment HbA1c; reduce total body weight by atleast 1% relative to pre-treatment body weight; reduce excess bodyweight by at least 3% relative to pre-treatment excess body weight;reduce mean blood pressure by at least 3% relative to pre-treatment meanblood pressure; and reduce total cholesterol by at least 3% relative topre-treatment total cholesterol.

FIG. 25 illustrates an upper gastrointestinal tract with a bleedingvascular lesion being treated by an ablation device, in accordance withan embodiment of the present specification. The vascular lesion is avisible vessel 2561 in the base of an ulcer 2562. The ablation catheter2563 is passed through the channel of an endoscope 2564. The conicalpositioning element 2565 is placed over the visible vessel 2561. Theconical positioning element 2565 has a known length ‘l’ and diameter‘d’, which are used to calculate the amount of thermal energy needed forcoagulation of the visible vessel to achieve hemostasis. The conicalpositioning element has an optional insulated membrane that preventsescape of thermal energy or vapor away from the disease site.

In one embodiment, the positioning attachment must be separated from theablation region by a distance of greater than 0.1 mm, preferably 1 mmand more preferably 1 cm. In one embodiment, the length ‘l’ is greaterthan 0.1 mm, preferably between 5 and 10 mm. In one embodiment, diameter‘d’ depends on the size of the lesion and can be between 1 mm and 10 cm,preferably 1 to 5 cm.

FIG. 26 is a flowchart illustrating a method of ablation of an upper GItract in accordance with one embodiment of the present specification.Referring to FIG. 26 , the first step 2601 includes inserting anendoscope into the upper gastrointestinal tract of a patient. Next, instep 2602, a catheter of an ablation device is passed through theendoscope, wherein the catheter includes a hollow shaft through which anablative agent can travel, at least one positioning element, at leastone input port for receiving an ablative agent, and at least oneinfusion port for delivering the ablative agent. The catheter is passedthrough the endoscope such that the positioning element is positionedproximate to the upper GI tract tissue to be ablated. In an embodiment,the ablation device includes a controller comprising a microprocessorfor controlling the delivery of the ablative agent. The positioningelement is deployed in the upper GI tract lumen of the patient such thatthe positioning element contacts a portion of the upper GI tract of thepatient and the catheter and infusion port are positioned within theupper GI tract lumen in step 2603. In one embodiment, the positioningelement is positioned over and encompasses the upper GI tract tissue.Finally, in step 2606, an ablative agent is delivered through theinfusion port to ablate the upper GI tract tissue.

Optionally, a sensor is used to measure at least one dimension of theupper GI tract in step 2604 and the measurement is used to determine theamount of ablative agent to be delivered in step 2605.

FIG. 27A is an illustration of pancreatic ablation being performed on apancreatic tumor 2765 in accordance with one embodiment of the presentspecification. The ablation device 2760 includes a needle 2761configured to be inserted into a lesion to deliver vapor for ablation.The ablation device 2760 is passed through a channel of an echoendoscope2763 which has been inserted into a gastrointestinal tract 2764 of apatient to view the patient's pancreas 2766. Vapor is delivered throughthe needle 2761 of the ablation device 2760 to ablate the pancreatictumor 2765.

FIG. 27B is a flowchart listing the steps involved in one embodiment ofa method of pancreatic ablation. At step 2770, an echoendoscope isadvanced proximate a pancreatic tissue. A pancreatic lesion to beablated is localized using the echoendoscope at step 2771. At step 2772,dimensions of the lesion are measured using the echoendoscope. One ofthe measured dimensions is used to calculate an amount of vapor todeliver at step 2773. The ablation needle is passed through a channel inthe echoendoscope and through a puncture in the gastrointestinal wallinto the pancreatic lesion at step 2774. At step 2775, suction isoptionally applied on the needle to aspirate fluid/cells from thelesion. Vapor is passed through the needle into the pancreatic lesion toheat the lesion while water is simultaneously circulated through anouter sheath of the needle to cool the puncture site at step 2776. Thearea of ablation is observed with the echoendoscope at step 2777. Thepassage of vapor is stopped once adequate ablation is achieved at step2778. At step 2779, the ablation needle is removed from theechoendoscope and the echoendoscope is removed from the patient.

FIG. 27C is a flowchart listing the steps involved in one embodiment ofa method of ablation of a pancreatic cyst. In step 2780, an endoscopicultrasound (EUS) is performed to define the size of the cyst. The sizeof the cyst is input into a microprocessor of a controller of anablation system in step 2781 to calculate the amount of ablative therapyto be provided. An echotip vapor delivery needle is placed into the cystunder EUS guidance in step 2782. In step 2783, some fluid is aspiratedfrom the cyst to decrease fluid volume of the cyst. One or more cyclesof vapor delivery are delivered to the cyst in step 2784 to heat fluidin the cyst to a temperature in a range of 45 to 100° C., ablating thelining of the cyst wall without significantly damaging the surroundingpancreatic tissue. Optionally, post-ablation fluid is aspirated from thecyst in step 2785. The needle is removed from the cyst in step 2786.

In various embodiments, ablation therapy provided by the vapor ablationsystems of the present specification is delivered to achieve thefollowing therapeutic endpoints for a tumor in or proximate the bileduct: maintain a tissue temperature of 100° C. or less; ablate at least50% of the surface area of a targeted cancer mucosa to a sufficientdepth such that after ablation a cross-sectional area improves by atleast 10% relative to a pre-treatment cross-sectional area; biliary flowimproves by at least 10% relative to pre-treatment biliary flow; tumorvolume decreases by at least 10% relative to a pre-treatment tumorvolume.

FIG. 28 is a flowchart listing the steps involved in one embodiment of amethod of tissue ablation in a bile duct. At step 2801, an endoscopicretrograde cholangiopancreatography (ERCP) is performed. Next in step2802, the bile duct is intubated with a cannula and a guide wire isplaced therein. In step 2803, the length of the bile duct segment to beablated is measured. The length is then input into a controller of anablation system to determine an amount of ablative therapy to provide instep 2804. In another embodiment, the length is used to select acatheter of appropriate ablation segment length. A catheter of theablation system is then passed through the ERCP channel over theguide-wire. The catheter includes a first positioning element, a secondpositioning element distal to the first positioning element, and aplurality of delivery ports positioned on the catheter between the firstand second positioning elements. The catheter is passed through the ERCPchannel such that the second first positioning element (balloon) isplaced distal to the bile duct to be ablated and the first positioningelement (balloon) is placed proximal to the bile duct to be ablated instep 2805. In step 2806, the two balloons are inflated to a set pressureP1 and the diameter of the bile duct is measured using a diameter ofeither of the two balloons or an average of the diameters of the twoballoons. The measured bile duct diameter is entered into thecontroller, either manually or automatically, and used to calculate thesurface area of the bile duct to be ablated in 2807. Thereafter, one ormore cycles of vapor is delivered to the bile duct through one or moreof the vapor delivery ports at a temperature in a range of 90 to 100° C.to ablate the bile duct tissue in 2808. In one embodiment, the balloonpressure is maintained during the delivery of ablative agent at apressure P₂ which is greater than or equal to pressure P1 in 2809.Optionally, the balloons are deflated to a pressure P3 which is lessthan or equal to P1 between the cycles of ablation in 2810. Theendoscope and the catheter are removed after the ablation is complete instep 2811.

Bronchial Ablation

Regarding pulmonary function, there are four lung volumes and four lungcapacities. A lung capacity consists of two or more lung volumes. Thelung volumes are tidal volume (VT), inspiratory reserve volume (IRV),expiratory reserve volume (ERV), and residual volume (RV). The four lungcapacities are total lung capacity (TLC), inspiratory capacity (IC),functional residual capacity (FRC), and vital capacity (VC). Measurementof the single-breath diffusing capacity for carbon monoxide (DLCO) is afast and safe tool in the evaluation of both restrictive and obstructivelung disease. Arterial blood gases (ABGs) are a helpful measurement inpulmonary function testing in selected patients. The primary role ofmeasuring ABGs in individuals that are healthy and stable is to confirmhypoventilation when it is suspected on the basis of medical history,such as respiratory muscle weakness or advanced COPD. Spirometryincludes tests of pulmonary mechanics such as measurements of forcedvital capacity (FVC), forced expiratory volume at the end of the firstsecond of forced expiration (FEV₁), forced expiratory flow (FEF) values,forced inspiratory flow rates (FIFs), and maximum voluntary ventilation(MVV). Measuring pulmonary mechanics assesses the ability of the lungsto move large volumes of air quickly through the airways to identifyairway obstruction.

In various embodiments, ablation therapy provided by the vapor ablationsystems of the present specification is delivered to achieve thefollowing therapeutic endpoints for pulmonary ablation: maintain atissue temperature at 100° C. or less; reduce TLC, defined as the volumein the lungs at maximal inflation, by at least 5% relative topre-treatment TLC; increase VT, defined as the volume of air moved intoor out of the lungs during quiet breathing, by at least 5% relative topre-treatment VT; decrease RV, defined as the volume of air remaining inthe lungs after a maximal exhalation, by 5% relative to pre-treatmentRV; increase ERV, defined as the maximal volume of air that can beexhaled from the end-expiratory position, by 5% relative topre-treatment ERV; increase IRV, defined as the maximal volume that canbe inhaled from the end-inspiratory level, by at least 5% relative topre-treatment IRV; increase IC by at least 5% relative to pre-treatmentIC; increase inspiratory vital capacity (IVC), defined as the maximumvolume of air inhaled from the point of maximum expiration, by at least5% relative to pre-treatment IVC; increase VC, defined as the volume ofair breathed out after the deepest inhalation, by at least 5% relativeto pre-treatment VC; decrease FRC, defined as the volume in the lungs atthe end expiratory position, by at least 5% relative to pre-treatmentFRC; decrease RV by at least 5% relative to pre-treatment RV; decreasealveolar gas volume (V^(A)) by at least 5% relative to pre-treatmentV^(A); no change in actual lung volume including the volume of theconducting airway (V^(L)) relative to pre-treatment V^(L); increase DLCOby at least 5% relative to pre-treatment DLCO; increase partial pressureof oxygen dissolved in plasma (PaO₂) by at least 2% and/or decreasepartial pressure of carbon dioxide dissolved in plasma (PaCO₂) by atleast 1% relative to pre-treatment PaO₂ and PaCO₂ levels; increase anyspirometry results by at least 5% relative to pre-treatment spirometryresults; increase FVC, defined as the vital capacity from a maximallyforced expiratory effort, by at least 5% relative to pre-treatment FVC;increase forced expiratory volume over time (FEV^(t)), defined as thevolume of air exhaled under forced conditions in the first t seconds, byat least 5% relative to pre-treatment FEV^(t); increase FEV₁ by at least5% relative to pre-treatment FEV₁; increase FEF by at least 5% relativeto pre-treatment FEF; increase FEF^(max), defined as the maximuminstantaneous flow achieved during a FVC maneuver, by at least 5%relative to pre-treatment FEF^(max); increase FIF by at least 5%relative to pre-treatment FIF; increase peak expiratory flow (PEF),defined as the highest forced expiratory flow measured with a peak flowmeter, by at least 5% relative to pre-treatment PEF; increase MVV,defined as the volume of air expired in a specified period duringrepetitive maximal effort, by at least 5% relative to pre-treatment MVV.

FIG. 29A is a flowchart illustrating a method of ablation ofbronchoalveolar tissue in accordance with an embodiment of the presentspecification. Referring to FIG. 29A, the first step 2901 includesinserting a bronchoscope into the bronchus of a patient. Next, in step2902, a catheter of an ablation device is passed through thebronchoscope, wherein the catheter includes a hollow shaft through whichan ablative agent can travel, at least one positioning element, and atleast one infusion port for delivering the ablative agent. In anembodiment, the ablation device includes a controller comprising amicroprocessor for controlling the delivery of the ablative agent. Thecatheter is inserted into the bronchoscope such that the positioningelement is positioned in a bronchus connected to a bullous cavitycomprising bronchial tissue to be ablated. The positioning element isdeployed such that it contacts a portion of the bronchus and thecatheter and infusion port are positioned proximate the bullous cavityin step 2903. In one embodiment, the bronchoscope is used as a fixationpoint to assist in positioning the catheter and the infusion port withinthe bullous cavity. Finally, in step 2904, an ablative agent isdelivered through the infusion port to ablate the bronchial tissue.

FIG. 29B is a flowchart illustrating a method of ablation of bronchialtissue in accordance with another embodiment of the presentspecification. Referring to FIG. 29B, the first step 2911 includesinserting a bronchoscope into the bronchus of a patient. Next, in step2912, a catheter of an ablation device is passed through thebronchoscope, wherein the catheter includes a hollow shaft through whichan ablative agent can travel, at least one first positioning element, atleast one second positioning element positioned distal to said at leastone first positioning element, and at least one infusion port fordelivering the ablative agent. In an embodiment, the ablation deviceincludes a controller comprising a microprocessor for controlling thedelivery of the ablative agent. The catheter is inserted into thebronchoscope such that the first positioning element is positioned in abronchus proximal to a bronchial tissue to be ablated and said secondpositioning element is positioned distal to said bronchial tissue to beablated. The positioning elements are deployed to contact the bronchusproximal and distal to the tissue to be ablated and the catheter andinfusion port are positioned proximate the tissue to be ablated in step2913. Finally, in step 2914, an ablative agent is delivered through theinfusion port to ablate the bronchial tissue.

Bronchial Thermoplasty

FIG. 30A illustrates a cross-sectional view of a catheter 3005 forperforming bronchial thermoplasty, in accordance with an embodiment ofthe present specification. The catheter 3005 includes an elongate body3010 having a proximal end and a distal end, and an inflatablemultilayer balloon 3015 at the distal end. In some embodiments, theelongate body 3010 has first, second and third lumens 3012, 3013, 3014.

The first lumen 3012 allows air to be pumped, from the proximal end,into the balloon 3015 for inflation. The second lumen 3013 accommodatesa heating element 3020 that may be a flexible heating chamber with aplurality of RF electrodes. Saline/water is allowed to be pumped, fromthe proximal end, into the second lumen 3013 to enter the heatingelement 3020 for conversion into steam/vapor. The third lumen 3014allows saline/water to flow out from the proximal end.

The multilayer balloon 3015 comprises of outer and inner balloon layersfused together. A plurality of fluid channels or paths 3022 are definedand sandwiched between the outer and inner layers. The channels 3022 arein fluid communication with the second and third lumens 3013, 3014 suchthat steam/vapor generated in the second lumen 3013 circulates throughthe channels 3022 and flows out of the catheter through the third lumen3014. During operation, the balloon 3015 is inflated to contact targettissue and steam/vapor is allowed to circulate through the channels 3022to create a deep burn in the target tissue without scarring. Thisresults in steam non-contiguously spreading over the tissue area in amanner that is controlled and can be circulated.

In various embodiments, the channels 3022 are configured into aplurality of patterns (such as, but not limited to, a wave, series oflines, sine wave, square wave) such that the circulating steam/vaporcreates ablation proximate the area of the channels 3022 without anyablation in the remaining area (that is, area devoid of the channels3022) of the balloon 3015. In embodiments, the balloon 3022 is activelyair-cooled to control a volume of tissue ablated. In variousembodiments, the catheter 3005 has a plurality of applications in nerveor muscle ablation in hollow organs where circumferential ablation isnot needed—such as, for example, in PV (Pulmonary Vein) ablation(heart), Renal Denervation (Hypertension) and Hepatic Vein Ablation(Diabetes). In an exemplary application of PV ablation, the channels3022 create a pattern of ablation in a PV sufficient to block conductionof electrical activity from a PV to a Left Atrium (LA) without causing asignificant stricture in the PV, wherein a length of the circumferentialpattern of ablation is greater than the circumference of the PVproximate the ablation. In some embodiments, a distance between twoadjacent circumferential ablation patterns is greater than two times thethickness of the PV.

FIG. 30B illustrates a plurality of patterns of the channels 3022, inaccordance with various embodiments of the present specification. Thefigure shows first, second, third, fourth, fifth, sixth and seventhexemplary patterns 3031, 3032, 3033, 3034, 3035, 3036, 3037. For each ofthe patterns, a first path 3040 shows a direction of flow of steam/vaporwhile a second path 3045 shows a direction of flow of water/saline out.The patterns of the channels 3022 determine the ablation pattern.

FIG. 30C illustrates a workflow for performing a bronchial thermoplastyprocedure using the catheter 3005, in accordance with an embodiment ofthe present specification. At step 3050 an endoscope tube 3052 isinserted into a patient's lung to position proximate a target tissuearea for ablation. At step 3055, the catheter 3005 is inserted through aworking channel of the endoscope 3052 such that the balloon 3015 ispositioned at the target tissue area. Thereafter, at step 3060, theballoon 3015 is inflated with air such that the balloon 3015 contactsthe target tissue area. Steam/vapor is now circulated through thepatterned channels 3022 of the balloon to ablate the target tissue area.

Lung Volume Reduction

FIG. 31A illustrates a lung volume reduction (LVR) catheter 3105 whileFIG. 31B illustrates the LVR catheter 3105 deployed through anendoscope/bronchoscope 3110, in accordance with embodiments of thepresent specification. Referring now to FIGS. 31A, 31B, the catheter3105 includes an elongate shaft 3115 having a proximal end and a distalend. The distal end has at least one vapor delivery port 3120 and aplurality of suction ports 3125. A positioning element 3122 is locatedproximate the at least one vapor delivery port 3120. In someembodiments, the positioning element 3122 is an inflatable balloon.

In some embodiments, the elongate shaft 3115 has first and second lumens3130, 3132 extending from the proximal end to the distal end. The firstlumen 3130 accommodates a heating element 3135 such as a flexibleheating chamber comprising a plurality of RF electrodes of the presentspecification. Saline/water enters the proximal end to reach the heatingelement 3135 where it is converted to steam/vapor for delivery throughthe at least one vapor delivery port 3120. The second lumen 3132 is influid communication with the plurality of suction ports 3125. Duringoperation, vapor is delivered through the at least one vapor deliveryport 3120 and air is suctioned in through the plurality of suction ports3125 thereby producing circulation of thermal energy between the vapordelivery port 3120 and the suction ports 3125. In an embodiment, a thirdlumen (not shown) allows air to be pumped into the balloon 3122 forinflation. FIG. 31B shows the catheter 3105 deployed through a workingchannel of the endoscope 3110.

In some embodiments, the at least one vapor delivery port 3120 is atleast 1 cm apart from a closest of the plurality of suction ports 3125.

FIG. 31C is a workflow for performing lung volume reduction using thecatheter 3105, in accordance with an embodiment of the presentspecification. At step 3150, diseased region is identified for ablationtherapy. At step 3152, the bronchoscope 3110 is positioned into theairway of the diseased region. At step 3154, the catheter 3105 isdeployed through a working channel of the bronchoscope 3110 such thatthe catheter 3105 is positioned proximate the diseased region. At step3156, the balloon 3122 is inflated, steam/vapor is delivered to thediseased region (through the vapor delivery port 3120) for a predefinedperiod of time, such as 3 to 10 seconds (depending upon the mass of thediseased region), while air is suctioned in through the suction ports3125.

FIG. 32A illustrates a needle catheter 3200 incorporating one flexibleheating chamber 130 of FIGS. 1A through 1D, in accordance with anembodiment. FIG. 32B illustrates a needle catheter 3220 incorporatingtwo flexible heating chambers 130, in accordance with an embodiment.Referring now to FIGS. 32A and 32B, the catheters 3200, 3220 eachcomprise an elongate body 3205, 3225 having a proximal end and a distalend. The bodies 3205, 3225 each have a lumen along their length and atleast one needle 3210, 3230 at their distal ends. In some embodiments,the needle is retractable. In an embodiment, at least one infusion port3215, 3235 is positioned proximate a proximal end of the needle 3210,3230, or on the needle 3210, 3230, which may be hollow. In variousembodiments, the at least one infusion port 3215, 3235 is positioned ina range of 1 mm to 50 cm from the heating chamber(s) 130. In variousembodiments, the needle catheters 3200, 3220 comprise any of the needleembodiments discussed in the present specification. At least one heatingchamber 130 is incorporated in the catheters 3200, 3220 proximate thedistal end of the bodies 3205, 3225. The embodiment of FIG. 32Aillustrates one heating chamber 130 while the embodiment of FIG. 32Billustrates two heating chambers 130 arranged in series. Referring toFIG. 32B, a water pump 3240, coupled to the proximal end of the body3225, supplies water/saline to a proximal end of the heating chambers130 through a lumen 3226 in the catheter body 3225. An RF generator 3245provides electrical current to a plurality of electrodes (such as,electrodes 136, 138) included in the heating chambers 130, which causessaid electrodes to generate heat, wherein said heat is transferred tosaid water/saline to convert the water/saline to vapor, which is thendelivered via infusion port 3235 to ablate a target tissue.

In some embodiments, the catheters 3200, 3220 may optionally include atleast one positioning element, such as an inflatable balloon, at thedistal end of the bodies 3205, 3225.

During use, the pump 3240 delivers water/saline to the proximal end ofthe heating chambers 130 while the RF generator 3245 causes theelectrodes to heat up and vaporize the water/saline flowing through theheating chambers 130. The generated vapor exits through the at least oneport 3235. The flexible heating chambers 130 impart improved flexibilityand maneuverability to the catheters 3200, 3220, allowing a physician tobetter position the catheters 3200, 3220 when performing needle ablationprocedures.

FIG. 32C is a flowchart illustrating one embodiment of a method ofablation of a tissue using the needle catheters 3200, 3220 of FIGS. 32Aand 32B. In the first step 3232, the catheter is inserted such that theat least one positioning element is positioned proximate to the tissueto be ablated. The next step 3234 involves extending the needle throughthe catheter such that the at least one infusion port is positionedproximate to the tissue. At step 3236, water/saline is provided to theheating chamber (to more than one heating chambers, in some embodiments)by operating the water pump. At step 3238, electric current is providedto electrodes of the heating chamber, using the RF generator, to convertwater/saline to vapor that exits the infusion ports to ablate thetissue. In another embodiment, the device does not include a positioningelement and the method does not include a step of positioning thepositioning element proximate the tissue to be ablated.

The above examples are merely illustrative of the many applications ofthe system of the present invention. Although only a few embodiments ofthe present invention have been described herein, it should beunderstood that the present invention might be embodied in many otherspecific forms without departing from the spirit or scope of theinvention. Therefore, the present examples and embodiments are to beconsidered as illustrative and not restrictive, and the invention may bemodified within the scope of the appended claims.

I claim:
 1. A multi-stage method for treating at least one of excessweight, obesity, eating disorders, metabolic syndrome, dyslipidemia,diabetes, polycystic ovarian disease, fatty liver disease, non-alcoholicfatty liver disease, or non-alcoholic steatohepatitis disease byablating duodenal tissue using a vapor ablation system, wherein thevapor ablation system comprises a controller having at least oneprocessor in data communication with at least one pump and a catheterconnection port in fluid communication with the at least one pump, themulti-stage method comprising: connecting a proximal end of a firstcatheter to the catheter connection port to place the first catheter influid communication with the at least one pump, wherein the firstcatheter comprises at least first and second positioning elementspositioned at first and second attachment points, respectively, on thecatheter and separated along a length of the first catheter and at leasttwo ports positioned between the at least first and second positioningelements, wherein each of the at least first and second positioningelements are of wire mesh cone or disc, and wherein each of the at leastfirst and second positioning elements has a first configuration and asecond configuration, and wherein, in the first configuration, each ofthe at least first and second positioning elements is compressed withinthe first catheter and in the second configuration, each of the at leastfirst and second positioning elements is expanded to be at leastpartially outside the first catheter; positioning the first catheterinside a patient such that, upon being expanded into the secondconfiguration, a distal one of the at least first and second positioningelements is positioned within in the patient's small intestine and aproximal one of the at least first and second positioning elements isproximally positioned more than 1 cm from the distal one of the at leastfirst and second positioning elements; expanding each of the at leastfirst and second positioning elements into their second configurations;activating the controller, wherein, upon activation, the controller isconfigured to cause the at least one pump to deliver saline into atleast one lumen in the first catheter and, wherein, upon activation, thecontroller is configured to cause an electrical current to be deliveredto at least one electrode positioned within the at least one lumen ofthe first catheter at a place different from said attachment points ofthe at least first and second positioning elements to the firstcatheter; delivering vapor through ports positioned in the firstcatheter between the at least first and second positioning elements,wherein said delivering vapor comprises delivering a first amount ofvapor for less than a therapeutic time, waiting a period of time topermit an edema to form, and, after said edema is formed, delivering asecond amount of vapor for the therapeutic time to ablate duodenaltissue; using the controller, shutting off the delivery of saline andelectrical current; removing the first catheter from the patient tocomplete a first stage of treating; waiting for at least six weeks;determining an efficacy of the first phase of treatment; depending onthe determined efficacy, connecting a proximal end of a second catheterto the catheter connection port to place the second catheter in fluidcommunication with the at least one pump, wherein the second cathetercomprises at least third and fourth positioning elements positioned atthird and fourth attachment points, respectively, on the catheter andseparated along a length of the second catheter and at least two portspositioned between the at least third and fourth positioning elements,wherein each of the at least third and fourth positioning elements areof wire mesh cone or disc, and wherein each of the at least third andfourth positioning elements has a first configuration and a secondconfiguration, and wherein, in the first configuration, each of the atleast third and fourth positioning elements is compressed within thesecond catheter and in the second configuration, each of the at leastthird and fourth positioning elements is expanded to be at leastpartially outside the second catheter; positioning the second catheterinside a patient such that, upon being expanded into the secondconfiguration, a distal one of the at least third and fourth positioningelements is positioned within in the patient's small intestine and aproximal one of the at least third and fourth positioning elements isproximally positioned more than 1 cm from the distal one of the at leastthird and fourth positioning elements; expanding each of the at leastthird and fourth positioning elements into their second configurations;activating the controller, wherein, upon activation, the controller isconfigured to cause the at least one pump to deliver saline into atleast one lumen in the second catheter and, wherein, upon activation,the controller is configured to cause an electrical current to bedelivered to at least one electrode positioned within the at least onelumen of the second catheter at a place different from said attachmentpoints of the at least third and fourth positioning elements to thesecond catheter; delivering vapor through ports positioned in the secondcatheter between the at least third and fourth positioning elements;using the controller, shutting off the delivery of saline and electricalcurrent; and removing the second catheter from the patient to complete asecond stage of treatment.
 2. The method of claim 1, wherein, in boththe first stage of treatment and second stage of treatment, the deliveryof saline and electrical current is automatically shut off after no morethan 60 seconds.
 3. The method of claim 1, further comprising, in boththe first stage of treatment and second stage of treatment, repeatedlyactivating the controller to deliver saline into the lumen andelectrical current to the at least one electrode using at least one of afoot pedal in data communication with the controller, a switch on thecatheter, or a switch on the controller.
 4. The method of claim 1,wherein, in both the first stage of treatment and second stage oftreatment, vapor is delivered such that an amount of energy in a rangeof 5 calories per second to 2500 calories per second is delivered. 5.The method of claim 1, wherein, in both the first stage of treatment andsecond stage of treatment, vapor is delivered such that an amount ofenergy in a range of 5 calories to 40 calories per gram of tissue to beablated is delivered.
 6. The method of claim 1, wherein, in both thefirst stage of treatment and second stage of treatment, vapor isdelivered such that at least fifty percent of a circumference of thesmall intestine is ablated.
 7. The method of claim 1, wherein, in thefirst stage of treatment, the at least first and second positioningelements, together with the small intestine, define an enclosed volumeand wherein at least one of the at least first and second positioningelements is positioned relative the small intestine to permit a flow ofair out of the enclosed volume when the vapor is delivered.
 8. Themethod of claim 1, wherein, in the second stage of treatment, the atleast third and fourth positioning elements, together with the smallintestine, define an enclosed volume and wherein at least one of the atleast third and fourth positioning elements is positioned relative thesmall intestine to permit a flow of air out of the enclosed volume whenthe vapor is delivered.
 9. The method of claim 1, wherein, in both thefirst state of treatment and second stage of treatment, the efficacy isdetermined by at least one of: a total body weight of the patientdecreases by at least 1% relative to a total body weight of the patientbefore ablation; an excess body weight of the patient decreases by atleast 1% relative to an excess body weight of the patient beforeablation; a total body weight of the patient decreases by at least 1%relative to a total body weight of the patient before ablation and awell-being level of the patient does not decrease more than 5% relativeto a well-being level of the patient before ablation; an excess bodyweight of the patient decreases by at least 1% relative to an excessbody weight of the patient before ablation and a well-being level of thepatient does not decrease more than 5% relative to a well-being level ofthe patient before ablation; a pre-prandial ghrelin level of the patientdecreases by at least 1% relative to a pre-prandial ghrelin level of thepatient before ablation; a post-prandial ghrelin level of the patientdecreases by at least 1% relative to a post-prandial ghrelin level ofthe patient before ablation; an exercise output of the patient increasesby at least 1% relative to an exercise output of the patient beforeablation; a glucagon-like peptide-1 level of the patient increases by atleast 1% relative to a glucagon-like peptide-1 level of the patientbefore ablation; a leptin level of the patient increases by at least 1%relative to a leptin level of the patient before ablation; the patient'sappetite decreases, over a predefined period of time, relative to thepatient's appetite before ablation; a peptide YY level of the patientincreases by at least 1% relative to a peptide YY level of the patientbefore ablation; a lipopolysaccharide level of the patient decreases byat least 1% relative to a lipopolysaccharide level of the patient beforeablation; a motilin-related peptide level of the patient decreases by atleast 1% relative to a motilin-related peptide level of the patientbefore ablation; a cholecystokinin level of the patient increases by atleast 1% relative to a cholecystokinin level of the patient beforeablation; a resting metabolic rate of the patient increases by at least1% relative to a resting metabolic rate of the patient before ablation;a plasma-beta endorphin level of the patient increases by at least 1%relative to a plasma-beta endorphin level of the patient beforeablation; an HbA1c level of the patient decreases by at least 0.3%relative to an HbA1c level of the patient before ablation; atriglyceride level of the patient decreases by at least 1% relative to atriglyceride level of the patient before ablation; a total bloodcholesterol level of the patient decreases by at least 1% relative to atotal blood cholesterol level of the patient before ablation; a glycemialevel of the patient decreases by at least 1% relative to a glycemialevel of the patient before ablation; a composition of the person's gutmicrobiota modulates from a first state before ablation to a secondstate after ablation, wherein the first state has a first level ofbacteroidetes and a first level of firmicutes, wherein the second statehas a second level of bacteroidetes and a second level of firmicutes,wherein the second level of bacteroidetes is greater than the firstlevel of bacteroidetes by at least 3%, and wherein the second level offirmicutes is less than the first level of firmicutes by at least 3%;or, a cumulative daily dose of the patient's antidiabetic medicationsdecreases by at least 10% relative to a cumulative daily dose of thepatient's antidiabetic medications before ablation.
 10. The method ofclaim 1, wherein, in both the first state of treatment and second stageof treatment, the efficacy is determined by at least one of: a lipidprofile of the patient improves by at least 10% relative a lipid profileof the patient before ablation, wherein lipid profile is defined atleast by a ratio of LDL cholesterol to HDL cholesterol, and improve isdefined as a decrease in the ratio of LDL cholesterol to HDLcholesterol; an LDL-cholesterol level of the patient decreases by atleast 10% relative to an LDL-cholesterol level of the patient beforeablation; or, a VLDL-cholesterol level of the patient decreases by atleast 10% relative to a VLDL-cholesterol level of the patient beforeablation.
 11. The method of claim 1, wherein, in both the first stage oftreatment and second stage of treatment, the efficacy is determined byat least one of: a 10% decrease in either ALT or AST levels relative toALT or AST levels before ablation; an absolute serum ferritin level ofless than 1.5 ULN (upper limit normal) relative to a serum ferritinlevel before ablation; less than 5% hepatic steatosis (HS) relative toan HS level before ablation, as measured on liver biopsy; less than 5%hepatic steatosis (HS) relative to an HS level before ablation, asmeasured by magnetic resonance (MR) imaging, either by spectroscopy orproton density fat fraction; at least a 5% improvement in an NAFLDFibrosis Score (NFS) relative to an NFS before ablation; at least a 5%improvement in an NAFLD Activity Score (NAS) relative to an NAS beforeablation; at least a 5% improvement in a Steatosis Activity Fibrosis(SAF) score relative to an SAF score before ablation; at least a 5%decrease in a mean annual fibrosis progression rate relative to a meanannual fibrosis progression rate before ablation, as measured byhistology, Fibrosis-4 (FIB-4) index, aspartate aminotransferase (AST) toplatelet ratio index (APRI), serum biomarkers (Enhanced Liver Fibrosis(ELF) panel, Fibrometer, FibroTest, or Hepascore), or imaging (transientelastography (TE), MR elastography (MRE), acoustic radiation forceimpulse imaging, or supersonic shear wave elastography); at least a 5%decrease in circulating levels of cytokeratin-18 fragments relative tocirculating levels of cytokeratin-18 fragments before ablation; at leasta 5% decrease in liver stiffness relative to liver stiffness beforeablation, as measured by vibration controlled transient elastography(VCTE/FibroScan); an improvement in NAS by at least 2 points, with atleast 1-point improvement in hepatocellular ballooning and at least1-point improvement in either lobular inflammation or steatosis score,and no increase in the fibrosis score, relative to NAS, hepatocellularballooning, lobular inflammation, steatosis, and fibrosis scores beforeablation; at least a 5% improvement in NFS scores relative to NFS scoresbefore ablation; or, at least a 5% improvement in any of the abovelisted NAFLD parameters as compared to a sham intervention or a placebo.12. A multi-stage method for treating cancerous or precancerousesophageal tissue by ablating the cancerous or precancerous esophagealtissue using a vapor ablation system, wherein the vapor ablation systemcomprises a controller having at least one processor in datacommunication with at least one pump and a catheter connection port influid communication with the at least pump, the multi-stage methodcomprising: connecting a proximal end of a first catheter to thecatheter connection port to place the first catheter in fluidcommunication with the at least one pump, wherein the first cathetercomprises at least first and second positioning elements positioned atfirst and second attachment points, respectively, on the catheter andseparated along a length of the first catheter and at least two portspositioned between the at least first and second positioning elements,wherein each of the at least first and second positioning elements areof wire mesh cone or disc, and wherein each of the at least first andsecond positioning elements has a first configuration and a secondconfiguration, and wherein, in the first configuration, each of the atleast first and second positioning elements is compressed within thefirst catheter and in the second configuration, each of the at leastfirst and second positioning elements is expanded to be at leastpartially outside the first catheter; positioning the first catheterinside a patient such that, upon being expanded into the secondconfiguration, a distal one of the at least first and second positioningelements is positioned adjacent the patient's esophagus and a proximalone of the at least first and second positioning elements is proximallypositioned more than 1 cm from the distal one of the at least first andsecond positioning elements; expanding each of the at least first andsecond positioning elements into their second configurations; activatingthe controller, wherein, upon activation, the controller is configuredto cause the at least one pump to deliver saline into at least one lumenin the first catheter and, wherein, upon activation, the controller isconfigured to cause an electrical current to be delivered to at leastone electrode positioned within the at least one lumen of the firstcatheter at a place different from said attachment points of the atleast first and second positioning elements to the first catheter;delivering vapor through ports positioned in the first catheter betweenthe at least first and second positioning elements, wherein saiddelivering vapor comprises delivering a first amount of vapor for lessthan a therapeutic time, waiting a period of time to permit an edema toform, and, after said edema is formed, delivering a second amount ofvapor for the therapeutic time to ablate duodenal tissue; using thecontroller, shutting off the delivery of saline and electrical current;removing the first catheter from the patient to complete a first stageof treating; waiting for at least six weeks; determining an efficacy ofthe first phase of treatment; depending upon the efficacy determination,connecting a proximal end of a second catheter to the catheterconnection port to place the second catheter in fluid communication withthe at least one pump, wherein the second catheter comprises a distaltip having at least one port and at least a third positioning elementpositioned at a third attachment point on the catheter attached to thedistal tip such that, wherein the at least third positioning element isof wire mesh cone or disc, and upon being in an operationalconfiguration, the at least third positioning element encircles the atleast one port and is configured to direct all vapor exiting from the atleast one port; positioning the second catheter inside the patient suchthat a distal surface of the at least third positioning element ispositioned adjacent the patient's esophagus; activating the controller,wherein, upon activation, the controller is configured to cause the atleast one pump to deliver saline into at least one lumen in the secondcatheter and, wherein, upon activation, the controller is configured tocause an electrical current to be delivered to at least one electrodepositioned within the at least one lumen of the second catheter at aplace different from said attachment point of the at least thirdpositioning element to the second catheter; delivering vapor through theat least one port positioned at the distal end of the second catheter;using the controller, shutting off the delivery of saline and electricalcurrent; and removing the second catheter from the patient to complete asecond stage of treatment.
 13. The method of claim 12, wherein, in boththe first stage of treatment and second stage of treatment, the deliveryof saline and electrical current is automatically shut off no more than60 seconds.
 14. The method of claim 12, further comprising, in both thefirst stage of treatment and second stage of treatment, repeatedlyactivating the controller to deliver saline into the lumen andelectrical current to the at least one electrode using at least one of afoot pedal in data communication with the controller, a switch on thecatheter, or a switch on the controller.
 15. The method of claim 12,wherein, in both the first stage of treatment and second stage oftreatment, vapor is delivered such that an amount of energy in a rangeof 5 calories per second to 2500 calories per second is delivered. 16.The method of claim 12, wherein, in both the first stage of treatmentand second stage of treatment, vapor is delivered such that an amount ofenergy in a range of 5 calories to 40 calories per gram of tissue to beablated is delivered.
 17. The method of claim 12, wherein, in both thefirst stage of treatment and second stage of treatment, vapor isdelivered such that at least fifty percent of a circumference of thesmall intestine is ablated.
 18. The method of claim 12, wherein, in thefirst stage of treatment, the at least first and second positioningelements, together with the esophageal tissue, define an enclosed volumeand wherein at least one of the at least first and second positioningelements is positioned relative the esophageal tissue to permit a flowof air out of the enclosed volume when the vapor is delivered.
 19. Themethod of claim 12, wherein, in the second stage of treatment, the atleast third positioning element, together with the esophageal tissue,defines an enclosed volume and wherein the at least third positioningelement is positioned relative the esophageal tissue to permit a flow ofair out of the enclosed volume when the vapor is delivered.